Prosthetic Valves And Related Inventions

ABSTRACT

This invention relates to the design and function of a compressible valve replacement prosthesis, collared or uncollared, which can be deployed into a beating heart without extracorporeal circulation using a transcatheter delivery system. The design as discussed focuses on the deployment of a device via a minimally invasive fashion and by way of example considers a minimally invasive surgical procedure preferably utilizing the intercostal or subxyphoid space for valve introduction. In order to accomplish this, the valve is formed in such a manner that it can be compressed to fit within a delivery system and secondarily ejected from the delivery system into the annulus of a target valve such as a mitral valve or tricuspid valve.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.17/231,085, filed Apr. 15, 2021, which is a continuation of U.S. patentapplication Ser. No. 16/594,263, filed Oct. 7, 2019, which is acontinuation of U.S. patent application Ser. No. 15/829,091, filed Dec.1, 2017, now U.S. Pat. No. 10,639,145, issued May 5, 2020, which is acontinuation of U.S. patent application Ser. No. 15/183,943, filed Jun.16, 2016, now U.S. Pat. No. 9,833,315, issued Dec. 5, 2017, which is adivisional of U.S. patent application Ser. No. 14/237,023, filed Feb. 4,2014, now U.S. Pat. No. 9,480,559, issued Nov. 1, 2016, which claimspriority under 35 U.S.C. § 371 to, and is a U.S. national phaseapplication of, International Application No. PCT/US2012/050579, filedAug. 13, 2012, which claims priority to and the benefit of U.S.Provisional Application Ser. No. 61/522,542, filed Aug. 11, 2011; U.S.Provisional Application Ser. No. 61/522,468, filed Aug. 11, 2011; U.S.Provisional Application Ser. No. 61/522,450, filed Aug. 11, 2011; U.S.Provisional Application Ser. No. 61/522,476, filed Aug. 11, 2011; U.S.Provisional Application Ser. No. 61/523,134, filed Aug. 12, 2011; U.S.Provisional Application Ser. No. 61/564,462, filed Nov. 29, 2011; andU.S. Provisional Application Ser. No. 61/615,264, filed Mar. 24, 2012,the disclosures of which are incorporated herein by reference in theirentireties.

BACKGROUND Field of the Invention

This invention relates to various improvements for prosthetic valves,including but not limited to transcatheter mitral valve replacementprosthetics and delivery devices therefor.

Background of the Invention

The current state of knowledge is as follows.

Valvular heart disease and specifically aortic and mitral valve diseaseis a significant health issue in the US. Annually approximately 90,000valve replacements are conducted in the US. Traditional valvereplacement surgery, the orthotopic replacement of a heart valve, is an“open heart” surgical procedure. Briefly, the procedure necessitatessurgical opening of the thorax, the initiation of extra-corporealcirculation with a heart-lung machine, stopping and opening the heart,excision and replacement of the diseased valve, and re-starting of theheart. While valve replacement surgery typically carries a 1-4%mortality risk in otherwise healthy persons, a significantly highermorbidity is associated to the procedure largely due to the necessityfor extra-corporeal circulation. Further, open heart surgery is oftenpoorly tolerated in elderly patients.

Thus, if the extra-corporeal component of the procedure could beeliminated, morbidities and the costs of valve replacement therapieswould be significantly reduced.

While replacement of the aortic valve in a transcatheter manner has beenthe subject of intense investigation, lesser attention has been focusedon the mitral valve. This is in part reflective of the greater level ofcomplexity associated to the native mitral valve apparatus and thus agreater level of difficulty with regards to inserting and anchoring thereplacement prosthesis.

Several designs for catheter-deployed (transcatheter) aortic valvereplacement are under various stages of development. The Edwards SAPIENtranscatheter heart valve is currently undergoing clinical trial inpatients with calcific aortic valve disease who are considered high-riskfor conventional open-heart valve surgery. This valve is deployable viaa retrograde transarterial (transfemoral) approach or an antegradetransapical (transventricular) approach. A key aspect of the EdwardsSAPIEN and other transcatheter aortic valve replacement designs is theirdependence on lateral fixation (e.g. tines) that engages the valvetissues as the primary anchoring mechanism. Such a design basicallyrelies on circumferential friction around the valve housing or stent toprevent dislodgement during the cardiac cycle. This anchoring mechanismis facilitated by, and may somewhat depend on, a calcified aortic valveannulus. This design also requires that the valve housing or stent havea certain degree of rigidity.

At least one transcatheter mitral valve design is currently indevelopment. The Endovalve uses a folding tripod-like design thatdelivers a tri-leaflet bioprosthetic valve. It is designed to bedeployed from a minimally invasive transatrial approach, and couldeventually be adapted to a transvenous atrial septotomy delivery. Thisdesign uses “proprietary gripping features” designed to engage the valveannulus and leaflets tissues. Thus the anchoring mechanism of thisdevice is essentially equivalent to that used by transcatheter aorticvalve replacement designs.

One problem involves the repetitive deformation of the nitinol wirematerial commonly used in the manufacture of stented valves. Fatiguefractures of the metal wire material can result in a catastrophicstructural failure whereby the valve support structure weakens andbreaks. Although failure of a single wire may not necessarily cause astructural collapse of the entire valve, over time, this possibilitybecomes a practical reality. When the consequence of valve failure meansthe death of the patient, the importance cannot be overstated.

Various problems continue to exist in this field, including problemswith perivalvular leaking around installed prosthetic valve, lack of agood fit and stability for the prosthetic valve within the native mitralannulus, atrial tissue erosion, excess wear on the metallic structures,interference with the aorta at the posterior side of the mitral annulus,difficulties in deployment and retrieval, and lack of customization, toname a few. Accordingly, there exists a need for the improvementinventions disclosed herein.

BRIEF SUMMARY OF THE INVENTION

The present invention relates to improvements for prosthetic valvesintended to be deployed into a closed beating heart using atranscatheter delivery system. The invention provides improvedstability, in-growth of the prosthetic, maintains structural integrityover large cycles, addresses biocompatibility issues, addressescommissural regurgitation, and addresses hemocompatibility issues.Additionally, the invention addresses problems related to unwantedbuckling of the material, lack of sealing of the prosthetic valve withinthe valvular annulus, unwanted twisting of fabrics, and difficultiesarising from elasticity during attachment of the cover to the stent.

Improved Surfaces

In a preferred embodiment, there is provided a multi-layer cover for aprosthetic heart valve having an expandable tubular stent and anexpandable internal leaflet assembly, wherein said stent is a tubularwire-form having an interior wall and an exterior wall, and wherein saidleaflet assembly is disposed within the stent to form a valve and iscomprised of stabilized tissue or synthetic material, wherein themulti-layer cover comprises at least two layers of stabilized tissue orsynthetic material, a first layer comprised of a polyester material anda second layer comprised of a polyester material or stabilized tissue,wherein the first layer is attached to the interior wall of the stentand the second layer is attached to the exterior wall of the stent.

In another preferred embodiment, there is provided wherein thestabilized tissue is derived from 30 day old bovine, ovine, equine orporcine pericardium, or from animal small intestine submucosa.

In another preferred embodiment, there is provided wherein the syntheticmaterial is selected from the group consisting of polyester,polyurethane, and polytetrafluoroethylene.

In another preferred embodiment, there is provided wherein the firstlayer and the second layer range in thickness from about 0.001″ (0.0254mm) to about 0.015″ (0.3809 mm), or more alternatively from about 0.002″(0.0508 mm) to about 0.010″ (0.254 mm), or alternatively wherein thefirst layer and the second layer are about 0.005″ (0.127 mm) inthickness.

In another preferred embodiment, there is provided wherein thestabilized tissue or synthetic material is treated with anticoagulant.

In another preferred embodiment, there is provided wherein thestabilized tissue or synthetic material is heparinized.

In another preferred embodiment, there is provided wherein the firstlayer and the second layer are both synthetic material.

In another preferred embodiment, there is provided wherein the syntheticmaterial is selected from the group consisting of polyester,polyurethane, and polytetrafluoroethylene.

In another preferred embodiment, there is provided wherein the syntheticmaterial is electrospun.

In another preferred embodiment, there is provided wherein the stenttubular wire-form is formed as a unitary shape comprising a tubular bodyportion having an open gasket-like sealing cuff at one end, and whereinthe tubular body portion and the sealing cuff are formed from the samepiece of superelastic metal, and wherein the first layer and the secondlayer extend to cover substantially all of the stent.

In another preferred embodiment, there is provided wherein thesuperelastic metal is a nickel-titanium alloy.

In another preferred embodiment, there is provided a prosthetic valvehaving the multi-layer cover described and/or claimed herein.

In another preferred embodiment, there is provided a method of treatingmitral regurgitation in a patient, which comprises the step ofsurgically deploying the prosthetic heart valve provided herein into themitral annulus of the patient.

In another preferred embodiment, there is provided a method of treatingtricuspid regurgitation in a patient, which comprises the step ofsurgically deploying the prosthetic heart valve provided herein into thetricuspid annulus of the patient.

Shuttlecock Annular Valve

In another embodiment, there is provided a prosthetic pericardial valvesupported by a self expanding nitinol body that uses tethers foranchoring to the ventricular myocardium.

In another preferred embodiment, there is provided a prostheticpericardial valve which comprises an expandable tubular stent having anannular collar and an internal leaflet assembly, wherein the stent iscovered on an exterior surface with stabilized tissue, synthetic fabricmaterial, or a combination of both, and the internal leaflet assembly isdisposed with the lumen of the stent and is comprised of stabilizedtissue, synthetic fabric material, or a combination of both, wherein theannular collar is a web of polyester or polyester-like fabric or metalmesh spanning from a distal end of the stent body to a collar supportstructure made from superelastic metal, the collar forming a flatcircular band connected on one edge to the stent and extendingcircumferentially around the exterior of the stent at or near a distalend of the stent.

In another preferred embodiment, there is provided a prostheticpericardial valve, wherein the internal leaflet assembly issaddle-shaped.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the stent covering is stabilized tissue.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the leaflet assembly is comprised ofstabilized tissue.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the prosthetic pericardial valve is elasticand is compressed into a delivery catheter for deployment within apatient, and whereby upon expelling the prosthetic pericardial valvefrom the delivery catheter, the valve expands to its functional shape.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the stent and collar support structure areformed from the same piece of superelastic metal.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the superelastic metal is a nickel-titaniumalloy.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the stent and collar are laser cut withpre-determined shapes to facilitate collapsing into a catheter deliverysystem.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the stent is constructed from ductile metalthat requires a balloon for expansion once the valve is positioned atthe valve annulus.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the stabilized tissue is derived from 30 dayold bovine, ovine, equine or porcine pericardium, or from animal smallintestine submucosa.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the synthetic material is selected from thegroup consisting of polyester, polyurethane, andpolytetrafluoroethylene.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the stabilized tissue or synthetic material istreated with anticoagulant.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the stabilized tissue or synthetic material isheparinized.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the angle of the collar to the stent comprisesa range of between about 5 and about 45 degrees.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the collar support structure extends laterallybeyond the wall of the expanded tubular stent between about 2 and about10 millimeters.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the tubular stent has a plurality of tetherattachment structures.

In another preferred embodiment, there is provided a prostheticpericardial valve further comprising a plurality of tethers attached tothe prosthetic pericardial valve for anchoring the prostheticpericardial valve to tissue.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein at least one of the plurality of tethers is anelastic tether.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein at least one of the plurality of tethers is abioresorbable tether.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein at least one of the plurality of tethers is apositioning tether and at least one of the plurality of tethers is ananchoring tether.

In another preferred embodiment, there is provided a prostheticpericardial valve further comprising at least one tether attached to thecollar support structure and at least one tether attached to the stentbody.

In another preferred embodiment, there is provided a prostheticpericardial valve further comprising a plurality of tethers attached tothe prosthetic pericardial valve wherein one of the plurality of tethersis attached to an epicardial tether securing device.

In another preferred embodiment, there is provided a prostheticpericardial valve wherein the leaflet assembly is constructed solely ofstabilized tissue or synthetic material without a separate wire supportstructure, wherein the leaflet assembly comprises a plurality of valveleaflets attached to a leaflet housing, wherein the leaflet assembly isdisposed within the lumen of the stent and is attached to the stent toprovide a sealed joint between the leaflet assembly and the inner wallof the stent.

In another preferred embodiment, there is provided wherein the valve hasa three-dimensional structure that is a D-shape in lateralcross-section.

In another preferred embodiment, there is provided wherein the valve hasa three-dimensional structure that is a kidney-shape in lateralcross-section.

In another preferred embodiment, there is provided a method of treatingmitral regurgitation in a patient, which comprises the step ofsurgically deploying the prosthetic pericardial valve disclosed andclaimed herein into the mitral annulus of the patient.

In another preferred embodiment, there is provided a method wherein theprosthetic pericardial valve is deployed by directly accessing thepericardial through the intercostal space, using an apical approach toenter the left ventricle, and deploying the prosthetic pericardial valveinto the mitral annulus.

In another preferred embodiment, there is provided a method wherein theprosthetic pericardial valve is deployed by directly accessing thepericardial through a thoracotomy, sternotomy, or minimally-invasivethoracic, thorascopic, or trans-diaphragmatic approach to enter the leftventricle.

In another preferred embodiment, there is provided a method wherein theprosthetic pericardial valve is deployed by directly accessing thepericardial through the intercostal space, using an approach through thelateral ventricular wall to enter the left ventricle.

In another preferred embodiment, there is provided a method wherein theprosthetic pericardial valve is deployed by accessing the left atrium ofthe pericardial using a transvenous atrial septostomy approach.

In another preferred embodiment, there is provided a method wherein theprosthetic pericardial valve is deployed by accessing the left ventricleof the pericardial using a transarterial retrograde aortic valveapproach.

In another preferred embodiment, there is provided a method wherein theprosthetic pericardial valve is deployed by accessing the left ventricleof the pericardial using a transvenous ventricular septostomy approach.

In another preferred embodiment, there is provided a method furthercomprising tethering the prosthetic pericardial valve to tissue withinthe left ventricle.

In another preferred embodiment, there is provided a method wherein theprosthetic pericardial valve is tethered to the apex of the leftventricle using an epicardial tether securing device.

In another preferred embodiment, there is provided a method wherein thetissue is selected from papillary muscle tissue, septal tissue, orventricular wall tissue.

In another preferred embodiment, there is provided a method wherein theprosthetic pericardial valve is tethered to the apex of the ventricularseptum.

In another preferred embodiment, there is provided a method of treatingtricuspid regurgitation in a patient, which comprises the step ofsurgically deploying the prosthetic pericardial valve as disclosed andclaimed herein into the tricuspid annulus of the patient.

In another preferred embodiment, there is provided a method wherein theprosthetic pericardial valve is deployed by directly accessing thepericardial through the intercostal space, using an apical approach toenter the right ventricle, or wherein the prosthetic pericardial valveis deployed by directly accessing the pericardial through a thoracotomy,sternotomy, or minimally-invasive thoracic, thorascopic, ortrans-diaphragmatic approach to enter the right ventricle, or whereinthe prosthetic pericardial valve is deployed by directly accessing thepericardial through the intercostal space, using an approach through thelateral ventricular wall to enter the right ventricle, or wherein theprosthetic pericardial valve is deployed by accessing the right atriumof the pericardial using a transvenous approach.

In another preferred embodiment, there is provided a method furthercomprising tethering the prosthetic pericardial valve to tissue withinthe right ventricle.

In another preferred embodiment, there is provided a method wherein theprosthetic pericardial valve is tethered to the apex of the rightventricle using an epicardial tether securing device.

In another preferred embodiment, there is provided a method wherein thetissue is selected from papillary muscle tissue, septal tissue, orventricular wall tissue.

Spring Anchor

In one embodiment, spring-shaped anchor comprising at least two coils,with shape-memory characteristics fashioned for attachment to aprosthetic pericardial valve stent and circumnavigation of the chordaetendineae.

In a preferred embodiment, wherein the anchor is fabricated from one ormore of a group of shape-memory, surgical-grade alloys, including,without limitation, nickel-titanium, copper-zinc-nickel, orcopper-aluminium-nickel.

In another preferred embodiment, wherein the anchor is fabricated fromone or more of a group of shape-memory polymers or ceramics, including,without limitation, polyurethanes with ionic or mesogenic componentsmade by a prepolymer method, a block copolymer of polyethyleneterephthalate (PET) and polyethyleneoxide (PEO), block copolymerscontaining polystyrene and poly(1,4-butadiene), an ABA triblockcopolymer made from poly (2-methyl-2-oxazoline) and polytetrahydrofuran,and the ceramic Mn-doped (Pb, Sr)TiO3.

In another preferred embodiment, wherein the shape-memory materialforming the anchor has been drawn or formed into a wire or band.

In another preferred embodiment, wherein the wire is 0.012″nickel-titanium wire.

In another preferred embodiment, wherein the wire or band, upondeployment, is formed to open into spring-like shape with an open tip.

In another preferred embodiment, wherein the proximal loop of the springanchor is fused to the base of the stent component of the associatedprosthetic pericardial valve via welding, soldering or by use of anadhesive.

In another preferred embodiment, wherein the adhesive used to bond theproximal loop of the spring anchor to the base of the stent is chosenfrom one or more of the following group, without limitation: syntheticpolymer glues including, without limitation, epoxy resins, epoxy putty,ethylene-vinyl acetate, phenol formaldehyde resins, polyamides,polyester resins, polypropylene, polysulfides, polyurethane, polyvinylacetate, polyvinyl alcohol, polyvinyl chloride, polyvinylpyrrolidone,silicones and styrene acrylic copolymer; synthetic monomer glues such asacrylnitrile, cyanoacrylate, acrylic and resorcinol glue; andsolvent-type glues such as polystyrene cement/butanone anddichloromethane.

In another preferred embodiment, wherein the loops of the coil equal orexceed the circumference of the base of the stent.

In another preferred embodiment, wherein all loops of the spring anchorare of equal circumference.

In another preferred embodiment, wherein the proximal loop of the springanchor is equal in circumference to the base of the prosthetic valvestent, further wherein each successive loop gradually increases incircumference.

In another preferred embodiment, further comprising wherein the fusedproximal loop of the spring anchor and base of the prosthetic valvestent are attached to a plurality of tethers for anchoring theprosthetic pericardial valve to tissue.

In another preferred embodiment, wherein the anchor is laser cut withpre-determined shapes to facilitate collapsing into a catheter deliverysystem.

In another preferred embodiment, wherein the anchor is covered withbiocompatible stabilized tissue or synthetic material.

In another preferred embodiment, wherein the stabilized covering tissueis derived from 30 day old bovine, ovine, equine or porcine pericardium,or from animal small intestine submucosa.

In another preferred embodiment, wherein the synthetic covering materialis selected from the group consisting of polyester, polyurethane, andpolytetrafluoroethylene.

In another preferred embodiment, wherein the stabilized tissue orsynthetic covering material is treated with anticoagulant.

In another preferred embodiment, wherein the stabilized tissue orsynthetic covering material is heparinized.

A method of treating mitral regurgitation in a patient, which comprisesthe step of surgically deploying a prosthetic pericardial valve into themitral annulus of the patient while simultaneously deploying the springanchor of claim 1 around the corresponding chordae tendineae.

In another preferred embodiment, the method wherein the prostheticpericardial valve and attached spring anchor are deployed by directlyaccessing the heart through the intercostal space, using an apicalapproach to enter the left ventricle, and deploying the prostheticpericardial valve into the mitral annulus and the spring anchor aroundthe chordae tendineae.

In another preferred embodiment, the method wherein the prostheticpericardial valve and attached spring anchor are deployed by directlyaccessing the heart through a thoracotomy, sternotomy, orminimally-invasive thoracic, thorascopic, or trans-diaphragmaticapproach to enter the left ventricle.

In another preferred embodiment, the method wherein the prostheticpericardial valve and attached spring anchor are deployed by directlyaccessing the heart through the intercostal space, using an approachthrough the lateral ventricular wall to enter the left ventricle.

In another preferred embodiment, the method wherein the prostheticpericardial valve and attached spring anchor are deployed by accessingthe left atrium of the pericardial using a transvenous atrial septostomyapproach.

In another preferred embodiment, the method wherein the prostheticpericardial valve and attached spring anchor are deployed by accessingthe left ventricle of the pericardial using a transarterial retrogradeaortic valve approach.

In another preferred embodiment, the method wherein the prostheticpericardial valve and attached spring anchor are deployed by accessingthe left ventricle of the pericardial using a transvenous ventricularseptostomy approach.

In another preferred embodiment, the method further comprising whereinthe spring anchor is secured around the chordae tendineae by guiding theanchor in a rotating motion using known transcatheter surgical tools.

In another preferred embodiment, the method further comprising whereinthe spring anchor is secured around the chordae tendineae by pulling thechordae tendineae within the circumference of one or more coil loopsusing known transcatheter surgical tools.

In another preferred embodiment, the method wherein the prostheticpericardial valve is tethered to one or more of the pericardial tissueareas, including without limitation, the apex of the left ventricle, thepapillary muscle tissue, the septal tissue, ventricular wall tissue,apex of the ventricular septum, using an epicardial tether securingdevice.

A method of treating tricuspid regurgitation in a patient, whichcomprises the step of surgically deploying a prosthetic pericardialvalve into the tricuspid annulus of the patient while simultaneouslydeploying the spring anchor of claim 1 around the corresponding chordaetendineae.

In another preferred embodiment, the method wherein the prostheticpericardial valve and attached spring anchor are deployed by directlyaccessing the pericardial through the intercostal space, using an apicalapproach to enter the right ventricle.

In another preferred embodiment, the method wherein the prostheticpericardial valve and attached spring anchor are deployed by directlyaccessing the pericardial through a thoracotomy, sternotomy, orminimally-invasive thoracic, thorascopic, or trans-diaphragmaticapproach to enter the right ventricle.

In another preferred embodiment, the method wherein the prostheticpericardial valve and attached spring anchor are deployed by directlyaccessing the pericardial through the intercostal space, using anapproach through the lateral ventricular wall to enter the rightventricle.

In another preferred embodiment, the method wherein the prostheticpericardial valve and attached spring anchor are deployed by accessingthe right atrium of the pericardial using a transvenous approach.

In another preferred embodiment, the method further comprising whereinthe spring anchor is secured around the chordae tendineae by guiding theanchor in a rotating motion using known transcatheter surgical tools.

In another preferred embodiment, the method further comprising whereinthe spring anchor is secured around the chordae tendineae by pulling thechordae tendineae within the circumference of one or more coil loopsusing known transcatheter surgical tools.

In another preferred embodiment, the method further comprising tetheringthe prosthetic pericardial valve to tissue within the right ventricle.

In another preferred embodiment, the method wherein the prostheticpericardial valve is tethered to the apex of the right ventricle usingan epicardial tether securing device.

In another preferred embodiment, the method wherein the tissue isselected from papillary muscle tissue, septal tissue, or ventricularwall tissue.

Annular Clamps

In one embodiment, a prosthetic valve clamp, comprising: (a) a hingemade of a pin, optionally surrounded by a spring, said pin extendingthrough holes in two interdigitated middle members, which hinge can bemanipulated into a closed or open position; (b) wherein each middlemember comprises (i) a footer section with a proximal side and a distalside, (ii) two flat plates wherein the distal end of each plate isattached to the narrow edges of the proximal side of the footer sectionand extend therefrom, in parallel, at adjustable angles, (iii) whereinthe proximal end of each such plate contains a centered circular hole ofa diameter to accommodate the insertion of the pin, and (iv) wherein aflat flange protrudes from the center of the inner end of the footersection, such flange containing a centered hole to allow apressure-bearing member to attach to open and close the hinge; (c) twoor more semicircular fingers, with an equal number of such fingersattached to the distal end of each middle member such that, upon closingof the hinge, the open side of the semicircle faces inward and theclosed side faces outward, wherein the fingers or dual sets of fingersmove towards one another as the hinge closes and away from one anotheras the hinge opens; (d) wherein the semicircular fingers are attached tothe middle member in a staggered fashion such that the semicircularmembers interdigitate upon closing; and (e) wherein the tip of eachsemicircular finger tapers to form a point capable of piercing valveannulus tissue.

In another preferred embodiment, a prosthetic valve clamp, comprising:(a) a hinge made of a pin, optionally surrounded by a spring, said pinextending through holes in the proximal ends of each of two or moreclosing members, which hinge can be manipulated into a closed or openposition; (b) two or more closing members, each with a straight basebranching outward into a semicircular shape such that, upon closing ofthe hinge, the open side of the semicircle faces inward and the closedside faces outward, wherein each closing member, or set of two or moreclosing members, move parallel to one another in opposite directions,towards one another as the hinge closes and away from one another as thehinge opens; (c) further comprising wherein the closing members areattached to the pin in a staggered fashion such that the semicircularmembers interdigitate upon closing; and (d) further comprising whereinthe tip of each closing member tapers to form a point capable ofpiercing valve annulus tissue.

In another preferred embodiment, a system for anchoring a prostheticmitral valve stent comprising: (a) a braided or laser-cut stent; (b) anassembly for a suction fin further comprising a tube located within theartificial stent annulus and circumnavigating said annulus, emanatingfrom the inner surface of the artificial stent annulus; (c) an assemblyfor a glue fin further comprising a tube located within the artificialstent annulus and circumnavigating said annulus, emanating from theinner surface of the artificial stent annulus; (d) a connection betweeneach of the glue fin assembly and the suction fin assembly and thetransapical delivery catheter; (e) a series of clamping devicesdispersed at intervals around the exterior surface of the artificialstent annulus, each clamping onto a security belt and opening upon theremoval of such belt; (f) a plurality of wires, with each attached tothe posterior side of a clamping device such that a pull on the wirewill close the clamping device; and (g) a guidance catheter wherein thewires of step (f) are contained within the catheter lumen that comprisesa plurality of holes circumnavigating the catheter, with one or morewires emanating from each such hole.

In another preferred embodiment, one of the above prosthetic valveanchoring devices, further comprising wherein the device is comprised ofone or more types of medically acceptable metallic alloys, natural orsynthetic polymers or ceramics, including but not limited toshape-memory alloys.

In another preferred embodiment, one of the above prosthetic valveanchoring devices, further comprising wherein the tapered tips of theelements comprise further anchoring features, including but not limitedto fishhook or arrowhead designs, with or without retractioncapabilities for ease in withdrawing the anchors from tissue.

Improved Cuff/Collar Variations

In one embodiment, an improved design and function of a compressibleprosthetic heart valve replacement having an improved contoured atrialcuff/collar which can be deployed into a closed beating heart using atranscatheter delivery system. The design as discussed focuses on thedeployment of a device via a minimally invasive fashion and by way ofexample considers a minimally invasive surgical procedure utilizing theintercostal or subxyphoid space for valve introduction. In order toaccomplish this, the valve is formed in such a manner that it can becompressed to fit within a delivery system and secondarily ejected fromthe delivery system into the target location, for example the mitral ortricuspid valve annulus.

In a preferred embodiment, there is provided a prosthetic mitral valvecontaining a atrial cuff/collar which locally contours to the mitralannulus.

In another preferred embodiment, there is provided a method of sealing adeployed prosthetic mitral valve against hemodynamic leaking, comprisingfitting a prosthetic mitral valve with an atrial cuff/collar prior todeployment wherein the atrial cuff/collar is constructed to contour tothe commissures of a pathologically defective mitral valve andconstructed to contour to the zone of coaptation of the pathologicallydefective mitral valve, wherein the atrial cuff/collar is formed fromwire originating from one end of an expandable tubular braided wirestent and the atrial cuff/collar is covered with stabilized tissue orsynthetic material, the commissural contour components of the atrialcuff/collar and the zone of coaptation contour components of the atrialcuff/collar forming a complete or partial saddle-shape wherein thecommissural contour components are in direct communication with themitral valve commissures, and the zone of coaptation contour componentsare in direct communication with the mitral valve zone of coaptation.

In a preferred embodiment, the atrial cuff/collar shape is agaricoid.

In another preferred embodiment, the atrial cuff/collar shape isonychoid.

In another preferred embodiment, the atrial cuff/collar shape isreniform.

In another preferred embodiment, the atrial cuff/collar shape is anoval.

In another preferred embodiment, the atrial cuff/collar shape is atruncated-oval having a squared end.

In another preferred embodiment, the atrial cuff/collar shape ispropeller-shaped having two or three blades.

In another preferred embodiment, the atrial cuff/collar shape iscruciform.

In another preferred embodiment, the atrial cuff/collar shape ispetal-shaped having flat radial covered loops.

In another preferred embodiment, the atrial cuff/collar shape isirregular or amoeboid.

In another preferred embodiment, the atrial cuff/collar shape iscotyloid shaped.

In another preferred embodiment, the atrial cuff/collar shape is apartial half-round fan-shape.

In another preferred embodiment, the atrial cuff/collar shape is arectangular U-shape.

In another preferred embodiment, the atrial cuff/collar is constructedfrom ductile metal.

In another preferred embodiment, the atrial cuff/collar shape isconstructed with a cover of stabilized tissue that is derived fromadult, or 90-day old, or 30 day old bovine, ovine, equine or porcinepericardium, or from animal small intestine submucosa.

In another preferred embodiment, the atrial cuff/collar shape isconstructed with a cover of synthetic material is selected from thegroup consisting of polyester, polyurethane, andpolytetrafluoroethylene.

In another preferred embodiment, the stabilized tissue or syntheticmaterial is treated with anticoagulant.

In another preferred embodiment, the method further comprises the stepof anchoring the prosthetic heart valve to tissue uses a plurality oftethers to the atrial cuff/collar.

In another preferred embodiment, at least one of the plurality oftethers is an elastic tether.

In another preferred embodiment, at least one of the plurality oftethers is a bioresorbable tether.

Improved Stent Designs

An embodiment relating to the design and function of a pre-configuredcompressible transcatheter prosthetic heart valve replacement havingimproved stent structure-function profiles which can be deployed into aclosed beating heart using a transcatheter delivery system. The designas discussed focuses on the deployment of a device via a minimallyinvasive fashion and by way of example considers a minimally invasivesurgical procedure utilizing the intercostal or subxyphoid space forvalve introduction. In order to accomplish this, the valve is formed insuch a manner that it can be compressed to fit within a delivery systemand secondarily ejected from the delivery system into the targetlocation, for example the mitral or tricuspid valve annulus.

In a preferred embodiment, there is provided a prosthetic mitral valvecontaining an improved stent which locally contours to the mitralstructures and/or annulus.

In another preferred embodiment, there is provided a prosthetic heartvalve with a stent body that has a low height to width profile.

In a preferred embodiment, the prosthetic mitral valve contains animproved stent body that is a half-round D-shape in cross-section.

In a preferred embodiment, the prosthetic mitral valve contains animproved stent body that is a bent tubular stent structure wherein thebend is directed away from the anterior leaflet, away from interferingwith coaptation of adjacent, e.g. aortic, valvular leaflets.

In a preferred embodiment, the prosthetic mitral valve contains animproved stent body that has a low height to width profile and theleaflet structure disposed within the stent is positioned at or near theatrial end of the stent body.

In another preferred embodiment, the a prosthetic mitral valve has astent body made from both braided wire (atrial end) and laser-cut metal(annular or ventricular end), or vice versa.

In a preferred embodiment, the prosthetic heart valve has a cuff thathas articulating wire loops of various lengths.

In another preferred embodiment, the prosthetic heart valve has at leastone elastic tether to provide compliance during the physiologic movementor conformational changes associated with heart contraction.

In another preferred embodiment, the prosthetic heart valve has a stentbody and cuff that are made from a superelastic metal.

In another preferred embodiment, the prosthetic heart valve has a tetherwhich is used to position the valve cuff into the mitral annulus toprevent perivalvular leak.

In another preferred embodiment, the tethers are bioabsorbable andprovide temporary anchoring until biological fixation of the prosthesisoccurs. Biological fixation consisting of fibrous adhesions between theleaflet tissues and prosthesis or compression on the prosthesis byreversal of heart dilation, or both.

In another preferred embodiment, the prosthetic heart valve has a cufffor a prosthetic heart valve, said cuff being covered with tissue.

In another preferred embodiment, the cuff is covered with a syntheticpolymer selected from expandable polytetrafluoroethylene (ePTFE) orpolyester.

In another preferred embodiment, there is provided a prosthetic heartvalve that has leaflet material constructed from a material selectedfrom the group consisting of polyurethane, polytetrafluoroethylene,pericardium, and small intestine submucosa.

In another preferred embodiment, there is provided a prosthetic heartvalve having surfaces that are treated with anticoagulant.

In another preferred embodiment, there is provided a prosthetic heartvalve having a cuff and containing anchoring tethers which are attachedto the cuff.

In another preferred embodiment, there is provided a prosthetic heartvalve having a cuff and containing anchoring tethers which are attachedto the cuff and at both commissural tips.

In another preferred embodiment, there is provided a prosthetic heartvalve having a cuff where the cuff attachment relative to the body iswithin the angles of about 60 degrees to about 150 degrees.

In another preferred embodiment, there is provided a prosthetic heartvalve containing a combination of tethers and barbs useful for anchoringthe device into the mitral annulus.

In another embodiment, the wire of the cuff is formed as a series ofradially extending loops of equal or variable length.

In another embodiment, the cuff extends laterally beyond the expandedtubular stent according to a ratio of the relationship between theheight of the expanded deployed stent (h) and the lateral distance thatthe cuff extends onto the tissue (l). Preferably, the h/l ratio canrange from 1:10 to 10:1, and more preferably includes without limitation1:3, 1:2, 1:1, 2:1, and fractional ranges there between such as1.25:2.0, 1.5:2.0, and so forth. It is contemplated in one non-limitingexample that the cuff can extend laterally (l) between about 3 and about30 millimeters.

In another embodiment, there is provided a feature wherein the tubularstent has a first end and a second end, wherein the cuff is formed fromthe stent itself, or in the alternative is formed separately and whereinthe cuff is located at the first end of the stent, and the second end ofthe tubular stent has a plurality of tether attachment structures.

In another embodiment, there is provided a feature further comprising aplurality of tethers for anchoring the prosthetic heart valve to tissueand/or for positioning the prosthetic heart valve.

In another embodiment, there is provided a feature further comprising anepicardial tether securing device, wherein the tethers extend from about2 cm to about 20 cm in length, and are fastened to an epicardial tethersecuring device. Some pathological conditions within a ventricle mayrequire a atrial-apical tether from about 8 to about 15 cm, or more asdescribed within the range above.

In another embodiment, there is provided a catheter delivery system fordelivery of a prosthetic heart valve which comprises a delivery catheterhaving the prosthetic heart valve disposed therein, and an obturator forexpelling the prosthetic heart valve.

In another embodiment, there is provided an assembly kit for preparingthe catheter delivery system which comprises a compression funnel, anintroducer, a wire snare, an obturator, a delivery catheter, and aprosthetic heart valve, wherein the compression funnel has an aperturefor attaching to the introducer, wherein said introducer is comprised ofa tube having a diameter that fits within the diameter of the deliverycatheter, wherein said obturator is comprised of a tube fitted with ahandle at one end and a cap at the other end, wherein said cap has anopening to allow the wire snare to travel therethrough, and saidobturator has a diameter that fits within the diameter of theintroducer, and wherein said prosthetic heart valve is compressible andfits within the delivery catheter.

In another embodiment, there is provided a method of treating mitralregurgitation and/or tricuspid regurgitation in a patient, whichcomprises the step of surgically deploying the prosthetic heart valvedescribed herein into the annulus of the target valve structure, e.g.mitral valve annulus and tricuspid valve annulus of the patient.

In another embodiment, there is provided a feature wherein theprosthetic heart valve is deployed by directly accessing the heartthrough an intercostal space, using an apical approach to enter the left(or right) ventricle, and deploying the prosthetic heart valve into thevalvular annulus using the catheter delivery system.

In another embodiment, there is provided a feature wherein theprosthetic heart valve is deployed by directly accessing the heartthrough a thoracotomy, sternotomy, or minimally-invasive thoracic,thorascopic, or transdiaphragmatic approach to enter the left (or right)ventricle, and deploying the prosthetic heart valve into the valvularannulus using the catheter delivery system.

In another embodiment, there is provided a feature wherein theprosthetic heart valve is deployed by directly accessing the heartthrough the intercostal space, using a lateral approach to enter theleft or right ventricle, and deploying the prosthetic heart valve intothe valvular annulus using the catheter delivery system.

In another embodiment, there is provided a feature wherein theprosthetic heart valve is deployed by accessing the left heart usingeither an antegrade-trans(atrial)septal(transvenous-trans(atrial)septal) approach or a retrograde(transarterial-transaortic) catheter approach to enter the left heart,and deploying the prosthetic heart valve into the mitral annulus usingthe catheter delivery system.

In another embodiment, there is provided a feature wherein theprosthetic heart valve is deployed into the mitral annulus from aretrograde approach by accessing the left ventricle through the apex ofthe ventricular septum (transvenous-trans(ventricular)septal approach).

In another embodiment, there is a feature wherein the prosthetic heartvalve is deployed into the mitral position using a retrogradetransventricular septal approach and the tethers are anchored into or onthe right ventricular side of the ventricular septum.

In another embodiment, there is provided a feature further comprisingtethering the prosthetic heart valve to tissue within the leftventricle.

In another embodiment, there is provided a feature wherein theprosthetic heart valve is tethered to the apex of the left ventricleusing an epicardial tether securing device.

In another embodiment, there is provided a retrieval method for quicklyremoving a prosthetic heart valve having one or more tethers from apatient using minimally invasive cardiac catheter techniques, whichcomprises the steps of, capturing the one or more tethers with acatheter having a snare attachment, guiding the captured tethers into acollapsible funnel attachment connected to the removal catheter, pullingthe tethers to conform the prosthetic heart valve into a collapsed,compressed conformation, and pulling the now compressed prosthetic heartvalve into the removal catheter for subsequent extraction. The retrievalmethod is contemplated for use for capturing the prosthetic heart valveas described herein or any suitable tethered, collapsible medicaldevice. In a preferred embodiment, the method is used to extract aprosthetic heart valve from either the left or right ventricle. Themethod may be particularly useful to extract the prosthetic applianceduring an aborted surgical deployment.

Narrow Gauge Stent

An embodiment relating to the design and function of a compressibleprosthetic heart valve replacement having a narrow-diameter stent body,which can be deployed into a closed beating heart using a transcatheterdelivery system. The design as discussed focuses on a prosthetic mitralvalve that fits within the native mitral valve annulus, but does notcompress or substantially interfere with the opening and closing of thenative commissural leaflets located at the terminus of the native mitralvalve leaflets.

As with previous devices, the deployment of this device is preferablyvia a minimally invasive surgical procedure utilizing percutaneous valveintroduction through the intercostal or subxyphoid space, but can alsobe an endoscopic catheter-based antegrade, retrograde, or trans-septaldeployment, as is know ion the arts. In order to accomplish this, thevalve is formed in such a manner that it can be compressed to fit withina delivery system and secondarily ejected from the delivery system intothe target location, for example the mitral or tricuspid valve annulus.

Accordingly, there is provided a method of deploying a prosthetic heartvalve for the treatment of commissural regurgitation and/or secondarymitral regurgitation in a patient in need thereof, which comprises thestep of using a cardiac imaging device to measure the diameter of thenative mitral annulus for selection and delivery of a prosthetic mitralvalve, the improvement consisting of using the same or different cardiacimaging device and measuring the distance from the posterior edge of theposterior leaflet to the anterior edge of the anterior leaflet and theposterior leaflet to define a cross-sectional leaflet diameter, whereinsaid cross-sectional leaflet diameter is substantially less than themaximum diameter of the mitral annulus, said maximum diameter defined asthe distance from the mitral annulus adjacent the anterolateralcommissure to the mitral annulus adjacent the posteromedial commissure.

In a preferred embodiment, there is provided for use herein a prosthetictranscatheter valve comprising an expandable tubular stent having a cuffand an expandable internal leaflet assembly, wherein the diameter ofsaid stent is less than the distance between the internal tips of thecommissural cusps, and wherein said leaflet assembly is disposed withinthe stent and is comprised of stabilized tissue or synthetic material.

In one preferred embodiment, there is also provided a prosthetic heartvalve as described herein wherein the diameter of the stent isapproximate to the distance between the interior tips of the commissuralcusps.

In another preferred embodiment, there is also provided a prostheticheart valve as described herein wherein the diameter of the stent isbetween 18 mm and 32 mm.

In another preferred embodiment, there is also provided a prostheticheart valve as described herein wherein the diameter of the stent isbetween 20 mm and 30 mm.

In another preferred embodiment, there is also provided a prostheticheart valve as described herein wherein the diameter of the stent isbetween 23 mm and 28 mm.

In another preferred embodiment, there is also provided a prostheticheart valve as described herein wherein the stent is sized to coverbetween 75% and 99% of the mitral valve area.

In another preferred embodiment, there is also provided a prostheticheart valve as described herein wherein the stent is sized to coverbetween 85% and 98% of the mitral valve area.

In another preferred embodiment, there is also provided a prostheticheart valve as described herein wherein the stent is sized to coverbetween 92% and 97% of the mitral valve area.

In another preferred embodiment, there is also provided a prostheticheart valve as described herein wherein the stent is sized to allow fora degree of mitral regurgitation of 20% or less.

In another preferred embodiment, there is also provided a prostheticheart valve as described herein wherein the stent is sized to allow fora degree of mitral regurgitation of 10% or less.

In another preferred embodiment, there is also provided a prostheticheart valve as described herein wherein the stent is sized to allow fora degree of mitral regurgitation of 5% or less.

In another preferred embodiment, there is also provided a cuff for anarrow gauge prosthetic heart valve for treatment of commissuralregurgitation and/or secondary mitral regurgitation, wherein the cuffhas an articulating structure made of a superelastic metal that iscovered with stabilized tissue or synthetic material, with only theportion of the cuff overlaying the commissures left uncovered.

In another preferred embodiment, there is also provided a method oftreating mitral secondary regurgitation in a patient, which comprisesthe step of surgically deploying the narrow gauge prosthetic heart valvedescribed herein into the mitral annulus of the patient.

In another preferred embodiment, there is also provided wherein theprosthetic heart valve is deployed by directly accessing the heartthrough the intercostal space, using an apical approach to enter theleft ventricle, and deploying the prosthetic heart valve into the mitralannulus, or wherein the prosthetic heart valve is deployed by directlyaccessing the heart through a thoracotomy, sternotomy, orminimally-invasive thoracic, thorascopic, or trans-diaphragmaticapproach to enter the left ventricle, or wherein the prosthetic heartvalve is deployed by directly accessing the heart through theintercostal space, using an approach through the lateral ventricularwall to enter the left ventricle, or wherein the prosthetic heart valveis deployed by accessing the left atrium of the heart using atransvenous atrial septostomy approach, or wherein the prosthetic heartvalve is deployed by accessing the left ventricle of the heart using atransarterial retrograde aortic valve approach, or wherein theprosthetic heart valve is deployed by accessing the left ventricle ofthe heart using a transvenous ventricular septostomy approach.

In another preferred embodiment, there is also provided a method whereinthe prosthetic heart valve is tethered to the apex of the left ventricleusing an epicardial tether securing device.

In another preferred embodiment, there is also provided a method oftreating commissural regurgitation and/or secondary mitral regurgitationby (1) measuring the area of the native valve and the regurgitantfraction using known imaging techniques; (2) sizing a prosthetic valveof claim 1 to allow between a 1% and 20% regurgitant fraction throughthe native commissures, based on the measures of step (1); and (3)implanting such prosthetic valve within the native mitral annulus.

BRIEF DESCRIPTION OF THE DRAWINGS

Improved Surfaces

FIG. 1 is a perspective view of a drawing showing one embodiment of aprosthetic valve according to the present invention.

FIG. 2 is a perspective cut-away view of a drawing showing the multiplelayered approach of the present invention.

FIG. 2A shows a three-layer construction of a portion of the valve ofFIG. 2.

FIG. 2B shows a three-layer construction, including specially treatedtissue, of a portion of the valve of FIG. 2.

FIGS. 3A-3C is a series of drawings showing non-limiting variations ofsandwiching treated tissue, stent, and synthetic material.

FIGS. 4A-4C is a series of electron micrographs showing the nanoporesand scale of the electrospun synthetic material which may be usedherein.

FIGS. 5A-5D is an exploded view showing detail of certain part of theinvention, especially tissue for the cuff, the bare wire body of thestent, a synthetic material layer, and an internal leaflet component.

FIG. 6 is a cut-away view of a heart with a delivery catheter containinga prosthetic valve according to the present invention and accessing theheart using an apical approach. FIG. 6 shows the delivery catheteradvanced to through the mitral valve and into the left atrium fordeployment of the prosthetic valve.

FIG. 7 is a cut-away view of a heart with a delivery catheter containinga prosthetic valve according to the present invention and accessing theheart using a lateral approach. FIG. 7 shows the delivery catheteradvanced to the mitral valve and into the left atrium for deployment ofthe prosthetic valve.

FIG. 8 is a cut-away view of a heart with a delivery catheter containinga prosthetic valve according to the present invention and accessing theright ventricle of the heart using an apical approach. FIG. 8 shows thedelivery catheter advanced through to the tricuspid valve and into theright atrium for deployment of the prosthetic valve.

FIGS. 9A-9D is a series of drawings illustrating how the valve isdeployed from the catheter.

FIG. 10 is a detailed sectional view of one embodiment of a prostheticvalve according to the present invention deployed within the annulus ofthe mitral valve of the heart and shows that it is anchored using (a)the atrial cuff and (b) the ventricular tethers connected to the apex,which are shown secured by a securing pledget.

FIG. 11 is a detailed side-perspective view of one embodiment of aprosthetic valve according to the present invention deployed within theannulus of the mitral valve of the heart and anchored using (a) theatrial cuff and (b) the ventricular tethers connected to papillarymuscles and/or ventricular wall and/or septum, which are each secured byone or more securing tissue anchors.

Shuttlecock Annular Valve

FIG. 12 is an illustration of a perspective view of a collared stentaccording to the present invention tethered to tissue within the leftventricle.

FIGS. 13A and 13B are illustrations of a side view showing how thecollar can originate at varying points on the exterior wall of the stentbody.

FIGS. 14A-14C are illustrations showing how the valve leaflets can varyand may include bicuspid/mitral and tricuspid embodiments.

FIG. 15 is a side view illustration showing how the stent body andcollar support structure may be covered with thin tissue, and how thecollar may be a web of elastic polymeric material spanning from thedistal end of the stent to the edge of the collar support structure.

FIG. 16 is a perspective view illustration of one embodiment of thepresent invention deployed with the mitral valve annulus, forming acomplete seal between the left atrium and ventricle, and showing how thecollar may be a mesh material spanning between an integratedstent-support structure assembly, and showing that a large number ofanchoring tethers are contemplated as within the scope of the presentinvention, including a tether to the apex of the left ventricle forattachment to a pledget on the pericardial surface.

FIG. 17 is a cut-away view of a heart with a delivery cathetercontaining a prosthetic valve according to the present invention andaccessing the heart using an apical approach. FIG. 17 shows the deliverycatheter advanced to through the mitral valve and into the left atriumfor deployment of the prosthetic valve.

FIG. 18 is a cut-away view of a heart with a delivery cathetercontaining a prosthetic valve according to the present invention andaccessing the heart using a lateral approach. FIG. 18 shows the deliverycatheter advanced to the mitral valve and into the left atrium fordeployment of the prosthetic valve.

FIG. 19 is a cut-away view of a heart with a delivery cathetercontaining a prosthetic valve according to the present invention andaccessing the right ventricle of the heart using an apical approach.FIG. 19 shows the delivery catheter advanced through to the tricuspidvalve and into the right atrium for deployment of the prosthetic valve.

FIGS. 20A-20D are illustrations of how the three-dimensional shape mayvary, including a D-shape and a kidney-bean-shaped valve.

Spring Anchor

FIG. 21 is an illustration of a perspective view of a spring-shapedanchor attached to a non-collared stent according to the presentinvention.

FIG. 22 is an illustration of a perspective view the spring-shapedanchor securing the attached stent into the mitral valve annulus of ahuman heart by rotatably fitting around the chordae tendineae.

FIGS. 23A-23C are illustrations showing how the valve leaflets can varyand may include bicuspid/mitral and tricuspid embodiments.

FIG. 24 is a perspective view illustration of one embodiment of thepresent invention emanating from a prosthetic valve deployed within themitral valve annulus, forming a complete seal between the left atriumand ventricle. FIG. 24 shows a collared version of a prosthetic valve,made from a mesh material spanning between an integrated stent-supportstructure assembly, and, in addition to the spring anchor deployed aboutthe chordae tendineae, further illustrates a plurality of anchoringtethers contemplated as within the scope of the present invention,including tethers to the apex of the left ventricle for attachment to apledget on the pericardial surface.

FIG. 25 is a cut-away view of a heart with a delivery cathetercontaining a prosthetic mitral valve and rotatably encircling thechordae tendineae with the spring anchor according to the presentinvention and accessing the heart using an apical approach into the leftventricle.

FIG. 26 is a cut-away view of a heart with a delivery cathetercontaining a prosthetic valve according to the present invention andaccessing the heart using a lateral approach. FIG. 26 shows the deliverycatheter advanced to the mitral valve and into the left atrium fordeployment of the prosthetic valve prior to deployment of the springanchor.

FIG. 27 is a cut-away view of a heart with a delivery cathetercontaining a prosthetic valve and spring anchor according to the presentinvention and accessing the right ventricle of the heart using an apicalapproach. FIG. 27 shows the delivery catheter advanced through to thetricuspid valve and into the right atrium for deployment of theprosthetic valve prior to deployment of the spring anchor.

Annular Clamps

FIG. 28A shows a perspective view of a braided wire stent with fourclamp-style annulus anchoring members located around the outside. FIG.28B shows a side view of the same braided wire stent with fourclamp-style annulus anchoring members.

FIG. 29 shows a side view of a clamp-style annulus anchoring member.

FIG. 30A shows a perspective view of a clamp-style annulus anchoringmember in the open position, comprising the following parts: pin,spring, two interdigitated middle members, two pairs of semicircularfingers, each with a tapered point. FIG. 30B shows a perspective view ofthe same clamp shown in FIG. 30A, but in the closed position with theends of the semicircular fingers interdigitated.

FIG. 31A shows a side view of the clamp-style annulus anchoring membershown in FIG. 30A, but with a pressure-bearing member attached to theflange portion of each middle member via the hole centered in suchflange, and exerting pressure to hold the clamp open. The pressurebearing members are emanating from a catheter in a straight position,exerting outward pressure on the clamp to hold it open. FIG. 31B shows apartially exploded view of the clamp and pressure bearing members,evidencing the holes centered in the middle member flanges and the maleattachment stud of each pressure bearing member. The figure shows themoment of release as the crimped point of the pressure bearing membersextend from their housing and cause the pressure bearing members torelease from the middle members of the clamp, thereby allowing thetorque of the spring to snap the clamp shut.

FIG. 32A shows a perspective view of a single semicircular finger, witha slot along the outer ridge and a series of triangular protrusionsalong one side for interlocking with another finger of the same design.FIG. 32B shows a side view of the same semicircular finger pictured inFIG. 32A.

FIG. 33A shows a perspective view of the outer and distal side of thecenter portion component of a middle member of the clamp assembly shownin FIG. 33A, with machine tooling slots and a ridged locking mechanismfor interlocking with other components of the clamp assembly. FIG. 33Bshows a perspective view of the inner and distal side of the same centerportion component pictured in FIG. 33A.

FIG. 34A shows a perspective view of a clamp assembly in the openposition, comprising a set of four closing members, each with a holebored directly into its proximal end through which a pin has beenthreaded, with the closing members interdigitated such that the firstand third closing members close in one direction while the second andfourth closing members close in the opposite direction. Each closingmember has a tapered distal tip. FIG. 34B shows the same assembly asFIG. 34A, but in the closed position.

FIG. 35A shows a side perspective of a clamp assembly in the openposition, comprising a set of four closing members, each with a holebored directly into its proximal end through which a pin has beenthreaded, with the closing members interdigitated such that the firstand third closing members close in one direction while the second andfourth closing members close in the opposite direction. Each closingmember has a tapered distal tip with a fish hook feature. FIG. 35B showsthe same assembly as FIG. 34A, from an angled perspective.

FIG. 36A shows a side view of the clamp assembly of FIG. 35A, but in aclosed position. FIG. 36B shows the same assembly as FIG. 36A, but froman angled perspective.

FIGS. 37A-37F show a variety of possible dimensions of variouscomponents of a clamp assembly.

FIG. 38 shows a braided stent with an annulus component comprising studassemblies for a suction fin and glue fin.

FIG. 39 shows a cross-section of the annulus component of the stent ofFIG. 38, evidencing two stable inner tubes for suction and applicationof glue.

FIG. 40 is a line drawing evidencing the angle of stent to grabber.

FIG. 41 is a perspective view from an underneath angle of a braidedstent around which a prosthetic annulus has been attached, furtherevidencing a series of clamping devices circumnavigating the prostheticannulus, each such device clamping down a security belt.

FIG. 42 evidences a perspective view of a guidance catheter locatedwithin the stent pictured in FIG. 41, with wires emanating from holesaround the catheter body and attached through the prosthetic annulus tothe clamp devices pictured in FIG. 41.

FIG. 43 shows a closer view of the guide catheter, stent and strings ofFIG. 42.

FIG. 44 shows an underneath view of the guidance catheter, string andstent assembly of FIGS. 41-43, evidencing the mechanism by which pullingthe strings through the catheter closes the clamp devices around thesecurity belt.

FIG. 45 shows a close view from a perspective inside the stent of theguidance catheter, string and stent assembly of FIGS. 41-44, evidencinga cross-section of the guidance catheter and a cross-section of theprosthetic annulus, evidencing the perforation of the prosthetic annulusby each string and the connection of each string to a clamping device.

Improved Cuff/Collar Variations

FIG. 46 is a perspective view of one embodiment of an improved atrialcuff/collar wherein the shape to the cuff/collar is agaricoid.

FIG. 47 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is onychoid.

FIG. 48 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is reniform.

FIG. 49 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is an oval.

FIG. 50 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is a truncated-oval having a squared end.

FIG. 51 is a perspective view of one embodiment showing the atrialcuff/collar as an acute angle sealing structure.

FIG. 52 is a perspective view of one embodiment showing the atrialcuff/collar and the internal valve leaflets at nearly that same planarlocation/height.

FIG. 53 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is propeller-shaped.

FIG. 54 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is is cruciform.

FIG. 55 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is petal-shaped having flat radial coveredloops.

FIG. 56 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is petal-shaped having flat radial coveredstellate loops.

FIG. 57 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is petal-shaped having flat radial coveredstellate loops illustrating how they can travel longitudinally toeffectuate sealing.

FIG. 58 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is is irregular or amoeboid.

FIG. 59 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is cotyloid shaped.

FIG. 60 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is a partial half-round fan-shape.

FIG. 61 is a perspective view of one embodiment showing the atrialcuff/collar wherein the shape is a upturned rectangular U-shape.

FIG. 62A is a side view and FIG. 62B is a front perspective view of oneembodiment showing the atrial cuff/collar attached to the stent body ata forward angle, posterior to anterior.

Improved Stent Designs

FIG. 63A is a perspective view of the saddle shape of a native mitralvalve leaflet structure or of a prosthetic valve leaflet structureaccording to the present invention.

FIG. 63B is a drawing of the three-dimensional relative position of themitral valve compared to the X-Y-Z axis.

FIG. 63C is a drawing of a side view representation of a mitral valveshowing the range of movement of the anterior and posterior leafletsfrom closed to opened.

FIG. 63D is a graphical three-dimensional representation of a mitralvalve with approximate orientation and sizes in all three dimensions.

FIG. 64 is a drawing of the heart in cross-section showing thepositional relationship of the mitral and tricuspid valves to thepulmonic and aortic arteries.

FIG. 65A is a perspective drawing of one embodiment according to thepresent invention showing a prosthetic mitral valve having akidney-shaped stent conformation in cross-section with an atrial cuff,shown here as opaque for stent detail.

FIG. 65B is a perspective drawing of one embodiment according to thepresent invention illustrating a prosthetic mitral valve having arounded-shape stent or oval-shape stent conformation in cross-sectionwith valve leaflets positioned towards the middle-point halfway upwithin the stent body, and with an atrial cuff, shown here as opaque forstent detail.

FIG. 66 is a perspective drawing of one embodiment according to thepresent invention showing a prosthetic mitral valve having acurved-tubular shape stent conformation in cross-section with an atrialcuff, shown here as opaque for stent detail.

FIG. 67 is a perspective drawing of one embodiment according to thepresent invention showing a prosthetic mitral valve having arounded-shape stent or oval-shape stent conformation in cross-sectionwith valve leaflets positioned high in the stent toward the atrial endof the stent body, and an atrial cuff, shown here as opaque for stentdetail.

FIG. 68 is a perspective drawing of one embodiment according to thepresent invention showing a prosthetic mitral valve having a stent bodymade from both braided wire (atrial end) and laser-cut metal (annular orventricular end), and an uncovered atrial cuff.

FIG. 69 is a perspective drawing of one embodiment according to thepresent invention showing a prosthetic mitral valve having a stent bodymade from both laser-cut metal (atrial end) and braided wire (annular orventricular end), and without an atrial cuff.

Narrow Gauge Stent

FIG. 70 is a line drawing showing a native mitral valve without implant.

FIG. 71 is a line drawing showing an implanted full-sized prostheticcausing commissural stretching.

FIG. 72 is a line drawing showing a prosthetic mitral valve sized toavoid interaction with or deformation of the commissures being used totreat mitral regurgitation at the central jet.

FIG. 73 is a line drawing showing a narrow diameter prosthetic bodyseated within a valve.

FIG. 74 is a line drawing showing how the hyperbolic paraboloid shape ofthe native mitral valve yields different diameters, whether posterior toanterior, or longitudinal along the line of the cusp interface.

FIG. 75 is a line drawing showing how an over-large valve extends beyondline c-c, and could, if the longest diameter were inadvertantly used,the full diameter of the native annulus line a-a, that it extends evenfurther beyond what is believed to be too large of a valve diameter (insome situations).

FIG. 76 and FIG. 77 are line drawings showing positive examples of theconcept disclosed herein, where the diameter is either equal to or lessthan the cross-section diameter of the native annulus from posterior toanterior side.

FIG. 78 is a line drawing showing an embodiment of the narrow valvewherein the dashed line illustrates the diameter of the native annulusand contrasts the narrow gauge stent seated within.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides various improvements in the design andcomponents of prosthetic valves, especially for use in cardiacsurgeries. Specifically, the invention relates to improved designs andfeatures providing better stability, fit, durability and ease ofdelivery and retrieval for such prosthetic valves. For the purposes ofthis application, the terms “collar” and “sealing cuff” are usedinterchangeably.

Improved Surface Components

In one embodiment, the invention provides improvement in the surfacecomponents and structures for prosthetic valves intended to be deployedinto a closed beating heart using a transcatheter delivery system. Thecombination of unique features herein addresses many of the issues andpoints of failure in current valve technology and provides a highlydeveloped approach to the extraordinary number of problems that arisewhen attempting to provide a medical device of this type. The inventionprovides improved in-growth of the prosthetic, maintains structuralintegrity over large cycles, addresses biocompatibility issues, andaddresses hemocompatibility issues. Additionally, the inventionaddresses problems related to unwanted buckling of the surface material,lack of sealing of the prosthetic valve within the valvular annulus,unwanted twisting of fabrics, and difficulties arising from elasticityduring attachment of the cover to the stent.

In a preferred embodiment, there is provided a multi-layer cover for aprosthetic heart valve having an expandable tubular stent and anexpandable internal leaflet assembly, wherein said stent is a tubularwire-form having an interior wall and an exterior wall, and wherein saidleaflet assembly is disposed within the stent to form a valve and iscomprised of stabilized tissue or synthetic material, wherein themulti-layer cover comprises at least two layers of stabilized tissue orsynthetic material, a first layer comprised of a polyester material anda second layer comprised of a polyester material or stabilized tissue,wherein the first layer is attached to the interior wall of the stentand the second layer is attached to the exterior wall of the stent.

Stabilized Tissue or Biocompatible Synthetic Material

In one embodiment, it is contemplated that multiple types of tissue andbiocompatible material may be used to line or cover both the inner“interior” and/or outer “exterior” lateral walls of the stent, and toline or cover embodiments utilizing the integral sealing cuff. As statedpreviously, the leaflet component may be constructed solely fromstabilized tissue or synthetic material, with or without using anadditional wire support, to create a leaflet assembly and valveleaflets. In this aspect, the leaflet component may be attached to thestent with or without the use of the wire form.

It is contemplated that the tissue may be used to cover the inside ofthe stent body, but that the outside of the stent body is lined orcovered with either tissue or synthetic material. Where the stent isheat formed to created a sealing cuff structure, the top “side” of thecuff wire form (formerly the interior until the stent was heat formed)will be lined with tissue, whereas the underside of the sealing cuffwill be lined, similar to the exterior, with tissue or more preferablysynthetic material

In one preferred embodiment, the tissue used herein is optionally abiological tissue and may be a chemically stabilized valve of an animal,such as a pig. In another preferred embodiment, the biological tissue isused to make leaflets that are sewn or attached to a metal frame. Thistissue is chemically stabilized pericardial tissue of an animal, such asa cow (bovine pericardium) or sheep (ovine pericardium) or pig (porcinepericardium) or horse (equine pericardium).

Preferably, the tissue is bovine pericardial tissue. Examples ofsuitable tissue include that used in the products Duraguard®,Peri-Guard®, and Vascu-Guard®, all products currently used in surgicalprocedures, and which are marketed as being harvested generally fromcattle less than 30 months old. Other patents and publications disclosethe surgical use of harvested, biocompatible animal thin tissuessuitable herein as biocompatible “jackets” or sleeves for implantablestents, including for example, U.S. Pat. No. 5,554,185 to Block, U.S.Pat. No. 7,108,717 to Design & Performance-Cyprus Limited disclosing acovered stent assembly, U.S. Pat. No. 6,440,164 to Scimed Life Systems,Inc. disclosing a bioprosthetic valve for implantation, and U.S. Pat.No. 5,336,616 to LifeCell Corporation discloses acellular collagen-basedtissue matrix for transplantation.

In one preferred embodiment, the synthetic material is a polyurethane orpolytetrafluoroethylene. The synthetic polymer materials includeexpanded polytetrafluoroethylene or polyester may optionally be used.Other suitable materials may optionally include thermoplasticpolycarbonate urethane, polyether urethane, segmented polyetherurethane, silicone polyether urethane, silicone-polycarbonate urethane,and ultra-high molecular weight polyethylene. Additional biocompatiblepolymers may optionally include polyolefins, elastomers,polyethylene-glycols, polyethersulphones, polysulphones,polyvinylpyrrolidones, polyvinylchlorides, other fluoropolymers,silicone polyesters, siloxane polymers and/or oligomers, and/orpolylactones, and block co-polymers using the same.

In another embodiment, the tissue and/or synthetic material liner/covermay optionally have a surface that has been treated with (or reactedwith) an anti-coagulant, such as, without limitation, immobilizedheparin. Such currently available heparinized polymers are known andavailable to a person of ordinary skill in the art.

Layers

In one preferred embodiment, the layering of the stent and the syntheticmaterial and tissue may be provided in various options. For example, inone preferred embodiment, it is contemplated that the interior layer(within the lumen of the stent) is Dacron® (aka PET), and the outerexterior of the stent is lined or covered with stabilized tissue asdescribed herein. In another embodiment, there is Dacron® both on theinterior and the exterior of the stent, where one or both may beelectrospun PET to provide the microscopic ‘hairs’ necessary forin-growth. In another embodiment, the prosthetic valve may have asynthetic layer on top of a tissue layer for an exterior, and have atissue layer on the interior.

Electrospun Fibers

Electrospinning is a technology that produces polymer fibers withdiameters ranging from the nano- to the microscale. Fabrics with complexshapes can be electrospun from solutions, producing a broad range offiber and fabric properties. Electrospinning produces materials withhigh surface to weight and volume ratios, which makes these materialsexcellent candidates for controlled biological interactions, especiallyconstruction of fibrous extra-cellular matrix scaffolds. The porousnature of the fabric coupled with the ability to spin many types ofpolymers allows for the formation of implantable structures. Here, theprosthetic valve cover material can use the electrospun fabric as ascaffolding to allow integration into the body, also known as in-growthor cell attachment (both endothelialization and smooth muscle cellattachment). Additives, ranging from therapeutic agents to propertymodifiers, can be introduced into the solutions and become incorporatedinto the fibers and fabrics.

In preferred embodiments, the synthetic material will range in thicknessfrom about 0.001″ (0.0254 mm) to about 0.015″ (0.3809 mm), or from about0.002″ (0.0508 mm) to about 0.010″ (0.254 mm), or alternatively whereinboth the first layer and the second layer are about 0.005″ (0.127 mm) inthickness. Preferred materials may be obtained from Zeus Co.,Orangeburg, S.C.

By creating a sandwiched prosthetic valve made using a nitinol (orsimilar) stent that has extremely thin tissue on the inside andextremely thin synthetic, e.g. Dacron®, on the outside, very small butvery durable prosthetic valves can be created and, importantly,delivered via the less-invasive, safer transcatheter deliverytechniques.

Synthetics and polymers contemplated as within the scope of the presentinvention support long-term cell growth, without cytotoxic or mutageniceffects, and have a degradation profile consistant with its usage. Forexample, the material should promote in-growth but not degrade prior toeffective in-growth, where the rate of degradation matches the rate oftissue attachment. Also, degradation by-products must be similarlynon-toxic and biocompatible.

Biodegradable materials contemplated as within the scope of the presentinvention include without limitation polyesters such as polylactide(PLA), polyglycolide (PGA), polycaprolactone (PCL),polylactide-co-polyglycolide (PLGA), co-polymers of poly-L-lactide andpolycaprolactone (PLLA-CL), andpoly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV). Also contemplated aswithin the scope of the invention are polyanhydrides, polyamides,modified polysaccharides, polyalkene glycols (e.g. PEG), polyalkeneoxides (e.g. PEO, PEO-co-PBT), and polyalkene terephthalates (e.g. PBT),and ethylene-vinyl acetate co-polymers.

However, non-degradable polymers may also be used but with biocompatiblecoatings in order to reduce problems known in the art that arise withthe use of certain polymers such as immune responses, thromboticresponses, and cell toxicity. include non-degradable materials such aspolytetrafluoroehtylene (PTFE), polyethylene-co-vinyl acetate, polyn-butyl methacrylate, poly(styrene-b-isobutylene-b-styrene,

The co-polymers may vary in the range of the ratio of one polymer to thecopolymer from a ratio of about 5:95 to a ratio of about 95:5. Incertain embodiments, the ratio range may be about 10:90 to about 90:10,or range from about 20:80 to 80:20, or from about 25:75 to 75:25, orfrom about 30:70 to 70:30, or 40:60 to 60:40, or 50:50, or subranges inbetween.

In a preferred non-limiting embodiment, the material is spun intonanofibers, fibers having a cross-sectional size of less than 1000 nm.Preferred diameters may range from about 100 to about 1000 nm.Alternative preferred embodiments include nanofibers having a diameterranging from about 200-800, or alternatively about 300-800 nm.

Additional therapeutic agents, e.g. sirolimus, paclitaxel, may be usedincorporated into the polymer in certain embodiments for local, timedrelease.

Fabrication of Electrospun Nanofibers

To fabricate polymeric nanofibers by electrospinning, the polymer wasdissolved in an appropriate solvent. The resultant solution was thenfilled in a syringe. With the aid of a syringe pump, the solution wasejected out through a needle tip with an inner diameter of 0.21 mm at aconstant feed-rate. A high DC voltage ranging from 10-15 kV (Gamma HighVoltage Research, Ormond Beach, Fla., USA) was applied between theneedle and a grounded aluminum plate which was 15 cm below the needle.

The electric field generated by the surface charge causes the solutiondrop at the tip of the needle to distort into the Taylor cone. Once theelectric potential at the surface charge exceeded a critical value, theelectrostatic forces overcome the solution surface tension and a thinjet of solution erupts from the surface of the cone. The parameters forfabrication of nanofibers include voltages from about 10-12.5 kV,solvents selected from hexafluoro-isopropanol, dimethyl-formamide,chloroform, methanol, dichloromethane, other solvents known to person ofskill in the polymer arts, and mixtures and combination thereof.

Manufacture of Ultra-thin Stabilized Tissue

In a preferred embodiment, ultra-thin vapor-cross linked stabilizedbioprosthetic or implant tissue material is contemplated. Tissue havinga 0.003′ (0.0762 mm) to about 0.010″ (0.254 mm) may be made using aprocess comprising the steps of: (a) vapor cross-linking a pre-digestedcompressed tissue specimen by exposing the tissue specimen to a vapor ofa cross-linking agent selected from the group consisting of aldehydes,epoxides, isocyanates, carbodiimides, isothiocyanates, glycidalethers,and acyl azides; and (b) chemically cross-linking the vapor-cross-linkedtissue specimen by exposing the vapor-crosslinked tissue specimen to anaqueous crosslinking bath for a predetermined time, such crosslinkingbath containing a liquid phase of a crosslinking agent selected from thegroup consisting of aldehydes, epoxides, isocyanates, carbodiimides,isothiocyanates, glycidalethers, and acyl azides. [para 15] Such tissuemay be porcine, ovine, equine or bovine in origin and preferably theinitial material is taken from a bovine animal 30 days old or less,although tissue from older animals is contemplated as within the scopeof the invention. In one preferred embodiment, the tissue specimen issubjected to chemical dehydration/compression and mechanical compressionbefore cross-linking.

Pre-digestion is provided by digesting a harvested, cleaned pericardialtissue in a solution containing a surfactant, such as 1% sodium laurelsulfate. The chemical dehydration/compression step comprises subjectingthe tissue specimen to hyperosmotic salt solution. And, the mechanicalcompression may be performed by subjecting the tissue specimen to aroller apparatus capable of compressing the tissue specimen to athickness ranging from about 0.003′ (0.0762 mm) to about 0.010″ (0.254mm).

The animal collagen tissue specimen is then chemically cross-linkedfirst by exposing the tissue to formaldehyde vapor for approximately 10minutes, and second by immersing the tissue in a glutaraldehyde solutionfor two consecutive sessions of approximately 24 hours each.

Functions of the Annular Cuff/Collar

The valve collar functions in a variety of ways. The first function ofthe prosthetic valve is to be a substitute for the native valve, butwith improved functions, such as inhibiting perivalvularleak/regurgitation of blood by flexing and sealing across the irregularcontours of the annulus and atrium.

The second function of the valve collar is to provide adjustability andcompliance once the prosthetic is seated.

The heart and its structures undergo complex conformational changesduring the cardiac cycle. For example, the mitral valve annulus has acomplex geometric shape known as a hyperbolic parabloid much like asaddle, with the horn being anterior, the seat back being posterior, andthe left and right valleys located medially and laterally. Beyond thiscomplexity, the area of the mitral annulus changes over the course ofthe cardiac cycle. Further, the geometry of the tricuspid valve andtricuspid annulus continues to be a topic of research, posing its ownparticular problems. Accordingly, compliance is a very important butunfortunately often overlooked requirement of cardiac devices.Compliance here refers to the ability of the valve to maintainstructural position and integrity during the cardiac cycle. Compliancewith the motion of the heart is a particularly important feature,especially the ability to provide localized compliance where theunderlying surfaces are acting differently from the adjacent surfaces.This ability to vary throughout the cardiac cycle allows the valve toremain seated and properly deployed in a manner not heretofore provided.

Additionally, compliance may be achieved through the use of the tetherswhere the tethers are preferably made from an elastic material.Tether-based compliance may be used alone, or in combination with thecollar-based compliance.

The third function of the valve/collar is to provide a valve that,during surgery, is able to be seated and be able to contour to theirregular surfaces of the atrium. The use of independent tethers allowsfor side to side fitting of the valve within the annulus. For example,where three tethers are used, they are located circumferentially about120 degrees relative to each other which allows the surgeon to observewhether or where perivalvular leaking might be occurring and to pull onone side or the other to create localized pressure and reduce oreliminate the leaking.

The forth function of the collar is to counter the forces that act todisplace the prosthesis toward/into the ventricle (i.e. atrial pressureand flow-generated shear stress) during ventricular filling.

Additional features of the collar include that it functions tostrengthen the leaflet assembly/stent combination by providingadditional structure. Further, during deployment, the collar functionsto guide the entire structure, the prosthetic valve, into place at themitral annulus during deployment and to keep the valve in place once itis deployed.

Another very important feature in one embodiment of the presentinvention is that the design of the valve allows the leaflets to belocated high within the stent body, in the top half (atrial) of thelumen of the stent, or even at or near the atrial top end of the stentportion of the prosthetic valve. By allowing the leaflets to be locatedhigh within the stent body, the reduces the occurrence of LVOTobstruction (Left Ventricular Outflow Tract obstruction), a situationwhere the blood leaving the left ventricle to the aortic valve isobstructed and/or has it's laminar flow disrupted. In some circumstancesthis pathological condition is caused by having a stent or other medicaldevice at or near the mitral valve area that extends too far into theleft ventricle itself.

Annular Cuff/Collar Structure

The collar is a substantially flat, circular, band-shaped collarstructure that is attached to and encircles the tubular stent forming aV-shape, when viewed in cross-section, between the exterior wall of thetubular stent and the flat, circular band-shaped annular expansiongasket. The stiff-yet-flexible nature of the attached (or integrated)gasket in a V-shape collar establishes a “cork” or “shuttlecock” type ofstructure that when the prosthetic valve is deployed into the annulus ofthe valve, e.g. mitral valve, the wedge-ring shape of the device, withits spring-like pusher band to provide a lateral annular compressivepressure or force against the native valve annulus to immobilize thevalve and provide a seal between the cardiac chambers, e.g. the atriumand the ventricular, to re-establish valve function via the prostheticvalve. As viewed from a side perspective, the collar diameter matchesthe diameter of the tubular stent where the collar is attached to thestent nearest the ventricle, but as the collar and stent wall form aV-shape, the diameter of the collar gets larger and larger, until itreaches it's maximum diameter at the atrial terminus of the collarpanel. As used herein, the term collar, inverted flange, gasket, springpanel, are considered to be functionally equivalent. When the tubularstent is pulled through the mitral valve aperture, the mitral annulus,by the tether loops in the direction of the left ventricle, the flexiblecollar acts as to stop the tubular stent from traveling any furtherthrough the mitral valve aperture. At this point, the entire prostheticvalve is held by lateral pressure caused by the forcible compression ofthe advancing spring-like collar through the mitral annulus, and thelongitudinal forces ventricular tethers attached to the left ventricle.

The collar is preferably formed from a web of polyester fabric spanningfrom the distal end of the stent body to a support structure made fromsuperelastic metal. Alternatively, the web made be made from a stiff,flexible shape-memory material such as the nickel-titanium alloymaterial Nitinol® wire that is covered by stabilized tissue or othersuitable biocompatible or synthetic material.

In one embodiment, the collar wire form is constructed from independentloops of wire creating lobes or segments extending axially around thecircumference of the bend or seam where the collar transitions to thetubular stent (in an integral collar) or where the collar is attached tothe stent (where they are separate, but joined components). The collarforms an acute angle in relation to the exterior wall of the tubularstent body.

In another embodiment, the collar is constructed from an attached panel.In this embodiment, the panel may be a solid metal band, or may beperforated, woven, or laser cut to provide a mesh-like surface, or maybe a polyester fabric material.

Because of the material's flexibility, the collar has the ability toarticulate back and forth, along the lateral axis compared to thelongitudinal axis that runs length-wise through the center of thetubular stent. In other words, where the metal has loops or is woven,the individual spindles or loops can independently move back and forth,and can spring back to their original position due to the relativestiffness of the wire. The collar has a certain modulus of elasticitysuch that, when attached to the wire of the stent, is able to allow thecollar to move. This flexibility gives the collar, upon being deployedwithin a patient's heart, the ability to conform to the anatomical shapenecessary for a particular application. In the example of a prostheticmitral valve, the collar is able to conform to the irregularities of theleft atrium and shape of the mitral annulus, and to provide a tight sealagainst the atrial tissue adjacent the mitral annulus and the tissuewithin the mitral annulus. As stated previously, this featureimportantly provides a degree of flexibility in sizing the a mitralvalve and prevents blood from leaking around the implanted prostheticheart valve.

In one preferred wire collar embodiment, the wire spindles of the collarare substantially uniform in shape and size. In another preferredembodiment of the present invention, each loop or spindle may be ofvarying shapes and sizes. In this example, it is contemplated that theloops may form a pattern of alternating large and small loops, dependingon where the valve is being deployed. In the case of a prosthetic mitralvalve, pre-operative imaging may allow for customizing the structure ofthe sealing cuff depending on a particular patient's anatomical geometryin the vicinity of the mitral annulus.

The sealing cuff wire form is constructed so as to provide sufficientstructural integrity to withstand the intracardiac forces withoutcollapsing. The sealing cuff wire form is preferably constructed of aweb of polyester fabric spanning from the distal end of the stent bodyto a support structure made from a superelastic metal, such as Nitinol™®and is capable of maintaining its function as a sealing collar for thetubular stent while under longitudinal forces that might cause astructural deformation or valve displacement. It is contemplated aswithin the scope of the invention to optionally use other shape memoryalloys such as Cu—Zn—Al—Ni alloys, and Cu—Al—Ni alloys. The heart isknown to generate an average left atrial pressure between about 8 and 30mm Hg (about 0.15 to 0.6 psi). This left atrial filling pressure is theexpected approximate pressure that would be exerted in the direction ofthe left ventricle when the prosthesis is open against the outer face ofthe collar as an anchoring force holding the collar against the mitralvalve annulus. The collar counteracts this downward longitudinalpressure against the prosthesis in the direction of the left ventricleto keep the valve from being displaced or slipping into the ventricle.In contrast, left ventricular systolic pressure, normally about 120 mmHg, exerts a force on the closed prosthesis in the direction of the leftatrium. The tethers counteract this force and are used to maintain thevalve position and withstand the ventricular force during ventricularcontraction or systole. Accordingly, the collar has sufficientstructural integrity to provide the necessary tension against thetethers without being dislodged and pulled into the left ventricle.Tethers and anchors may also be used to secure position against anyother directional forces as necessary. After a period of time, changesin the geometry of the heart and/or fibrous adhesion between prosthesisand surrounding cardiac tissues may assist or replace the function ofthe ventricular tethers in resisting longitudinal forces on the valveprosthesis during ventricular contraction.

Annular Clamp Structure and Function

It is possible for a prosthetic valve stent to be stabilized within thevalvular annulus through the use of integrated clamps located atintervals around the circumference of the stent. This clamp system mayuse clamps made of metal or similarly rigid and durable material, eitheras an integrated component of the stent during manufacture, bysoldering, by threading stent wire through anchoring apertures in theclamp structure, or a similar attachment process.

In one embodiment of a clamp-based anchoring system, each clampcomprises a hinge made of a pin, optionally surrounded by a spring, saidpin extending through holes in two interdigitated middle members, whichhinge could be manipulated into a closed or open position. Further, eachmiddle member of a clamp could comprise (a) a footer section with aproximal side and a distal side, (b) two flat plates with the distal endof each plate attached to the narrow edges of the proximal side of thefooter section and extending out, parallel to each other, at a diagonalangle, (c) the proximal end of each plate containing a centered circularhole of a diameter to accommodate the insertion of the pin, and (d) aflat flange protruding from the center of the inner end of the footersection, with the flange containing a centered hole to allow connectionby a tool to open and close the hinge. Attached to the distal end ofeach of the two middle members, two or more semicircular fingers, withan equal number of such fingers attached to each middle member suchthat, upon closing of the hinge, the open side of the semicircle facesinward and the closed side faces outward.

In this embodiment, the dual sets of semicircular fingers would movetowards one another as the hinge closes and away from one another as thehinge opens. The semicircular fingers are attached to the middle membersin a staggered fashion such that the semicircular members interdigitateupon closing. Finally, the tip of each semicircular finger tapers toform a point capable of piercing valve annulus tissue, allowing for afirm stabilizing anchor for both the stent and the valve it contains.

In a more preferred embodiment, the clamp assembly described above shallbe manufactured similar to the dimensions indicated in FIGS. 37A-37F.

The clamp of the immediately preceding embodiment may be comprisedwithin a clamp-based valve anchoring system in which two flexiblemembers, each with a preformed bend and protruding from a deliveryhousing, wherein each such flexible member is attached to the flange ofeach middle member, such that the flexible member is straightened uponretraction into the delivery housing, and the action of straighteningthe flexible member applies pressure to the two flanges, closing thehinge.

In another preferred embodiment, the clamp body would comprise a hingemade of a pin, optionally surrounded by a spring, said pin extendingthrough holes in the proximal ends of each of two or more closingmembers, which hinge can be manipulated into a closed or open position.The closing members each have a straight base branching outward into asemicircular shape so that, upon closing the hinge, the open side of thesemicircle faces inward and the closed side faces outward.

Each closing member, or set of two or more closing members, will moveparallel to one another in opposite directions, towards one another asthe hinge closes and away from one another as the hinge opens. Thus, anopen clamp can be positioned so that one or more closing members arelocated on either side of the native valve annulus tissue, and the tipswill contact the annulus tissue upon the clamp being moved to a closedposition.

Further, the closing members are attached to the pin in a staggeredfashion such that the semicircular members interdigitate upon closing;and the tip of each closing member tapers to form a point capable ofpiercing the valve annulus tissue, again allowing for a firm stabilizinganchor for both the stent and the valve it contains.

In a more preferred embodiment, the clamp assembly described above shallbe manufactured similar to the dimensions indicated in FIGS. 37A-37F.

Any of the clamps or other anchoring elements, or pressure-bearingmembers, described herein may be comprised of any surgically acceptablemetal, natural or synthetic polymer or ceramic material, including butnot limited to shape-memory alloys. The tapered tips of anchoringelements may also include further anchoring features, including but notlimited to fishhook or arrowhead designs, with or without retractioncapabilities for ease in withdrawing the anchors from tissue.

Functions of the Improved Annular Cuff/Collar

The atrial cuff or collar functions in a variety of ways. The firstfunction of the atrial cuff/collar is to inhibit perivalvularleak/regurgitation of blood around the prosthesis. By flexing andsealing across the irregular contours of the annulus and atrium, leakingis minimized and/or prevented.

The second function of the atrial cuff/collar is to provide anadjustable and/or compliant bioprosthetic valve. The heart and itsstructures undergo complex conformational changes during the cardiaccycle. For example, the mitral valve annulus has a complex geometricshape known as a hyperbolic parabloid much like a saddle, with the hornbeing anterior, the seat back being posterior, and the left and rightvalleys located medially and laterally. Beyond this complexity, the areaof the mitral annulus changes over the course of the cardiac cycle.Further, the geometry of the tricuspid valve and tricuspid annuluscontinues to be a topic of research, posing its own particular problems.Accordingly, compliance is a very important but unfortunately oftenoverlooked requirement of cardiac devices. Compliance here refers to theability of the valve to maintain structural position and integrityduring the cardiac cycle. Compliance with the motion of the heart is aparticularly important feature, especially the ability to providelocalized compliance where the underlying surfaces are actingdifferently from the adjacent surfaces. This ability to vary throughoutthe cardiac cycle allows the valve to remain seated and properlydeployed in a manner not heretofore provided.

Additionally, compliance may be achieved through the use of the tetherswhere the tethers are preferably made from an elastic material.Tether-based compliance may be used alone, or in combination with theatrial cuff/collar-based compliance.

The third function of the atrial cuff/collar and valve is to provide avalve that, during surgery, is able to be seated and be able to contourto the irregular surfaces of the atrium. The use of independent tethersallows for side to side fitting of the valve within the annulus. Forexample, where three tethers are used, they are locatedcircumferentially about 120 degrees relative to each other which allowsthe surgeon to observe whether or where perivalvular leaking might beoccurring and to pull on one side or the other to create localizedpressure and reduce or eliminate the leaking.

The fourth function of the atrial cuff/collar is to counter the forcesthat act to displace the prosthesis toward/into the ventricle (i.e.atrial pressure and flow-generated shear stress) during ventricularfilling.

Additional features of the atrial cuff/collar include that it functionsto strengthen the leaflet assembly/stent combination by providingadditional structure. Further, during deployment, the atrial cuff/collarfunctions to guide the entire structure, the prosthetic valve, intoplace at the mitral annulus during deployment and to keep the valve inplace once it is deployed. Another important function is to reducepulmonary edema by improving atrial drainage.

Structure of the Improved Cuff/Collar

The atrial cuff/collar is a substantially flat plate that projectsbeyond the diameter of the tubular stent to form a rim or border. Asused herein, the term atrial cuff/collar, cuff, flange, collar, bonnet,apron, or skirting are considered to be functionally equivalent. Whenthe tubular stent is pulled through the mitral valve aperture, themitral annulus, by the tether loops in the direction of the leftventricle, the atrial cuff/collar acts as a collar to stop the tubularstent from traveling any further through the mitral valve aperture. Theentire prosthetic valve is held by longitudinal forces between theatrial cuff/collar which is seated in the left atrium and mitralannulus, and the ventricular tethers attached to the left ventricle.

The atrial cuff/collar is formed from a stiff, flexible shape-memorymaterial such as the nickel-titanium alloy material Nitinol™ wire thatis covered by stabilized tissue or other suitable biocompatible orsynthetic material. In one embodiment, the atrial cuff/collar wire formis constructed from independent loops of wire that create lobes orsegments extending axially around the circumference of the bend or seamwhere the atrial cuff/collar transitions to the tubular stent (in anintegral atrial cuff/collar) or where the atrial cuff/collar is attachedto the stent (where they are separate, but joined components).

Once covered by stabilized tissue or material, the loops provide theatrial cuff/collar the ability to travel up and down, to articulate,along the longitudinal axis that runs through the center of the tubularstent. In other words, the individual spindles or loops canindependently move up and down, and can spring back to their originalposition due to the relative stiffness of the wire. The tissue ormaterial that covers the atrial cuff/collar wire has a certain modulusof elasticity such that, when attached to the wire of the atrialcuff/collar, is able to allow the wire spindles to move. Thisflexibility gives the atrial cuff/collar, upon being deployed within apatient's heart, the ability to conform to the anatomical shapenecessary for a particular application. In the example of a prostheticmitral valve, the atrial cuff/collar is able to conform to theirregularities of the left atrium and shape of the mitral annulus, andto provide a tight seal against the atrial tissue adjacent the mitralannulus and the tissue within the mitral annulus. As stated previously,this feature importantly provides a degree of flexibility in sizing thea mitral valve and prevents blood from leaking around the implantedprosthetic heart valve.

An additional important aspect of the atrial cuff/collar dimension andshape is that, when fully seated and secured, the edge of the atrialcuff/collar preferably should not be oriented laterally into the atrialwall such that it can produce a penetrating or cutting action on theatrial wall.

In one preferred embodiment, the wire spindles of the atrial cuff/collarare substantially uniform in shape and size. In another preferredembodiment of the present invention, each loop or spindle may be ofvarying shapes and sizes. In this example, it is contemplated that theloops may form a pattern of alternating large and small loops, dependingon where the valve is being deployed. In the case of a prosthetic mitralvalve, pre-operative imaging may allow for customizing the structure ofthe atrial cuff/collar depending on a particular patient's anatomicalgeometry in the vicinity of the mitral annulus.

The atrial cuff/collar wire form is constructed so as to providesufficient structural integrity to withstand the intracardiac forceswithout collapsing. The atrial cuff/collar wire form is preferablyconstructed of a superelastic metal, such as Nitinol™® and is capable ofmaintaining its function as a sealing collar for the tubular stent whileunder longitudinal forces that might cause a structural deformation orvalve displacement. It is contemplated as within the scope of theinvention to optionally use other shape memory alloys such asCu—Zn—Al—Ni alloys, and Cu—Al—Ni alloys. The heart is known to generatean average left atrial pressure between about 8 and 30 mm Hg (about 0.15to 0.6 psi). This left atrial filling pressure is the expectedapproximate pressure that would be exerted in the direction of the leftventricle when the prosthesis is open against the outer face of theatrial cuff/collar as an anchoring force holding the atrial cuff/collaragainst the atrial tissue that is adjacent the mitral valve. The atrialcuff/collar counteracts this longitudinal pressure against theprosthesis in the direction of the left ventricle to keep the valve frombeing displaced or slipping into the ventricle. In contrast, leftventricular systolic pressure, normally about 120 mm Hg, exerts a forceon the closed prosthesis in the direction of the left atrium. Thetethers counteract this force and are used to maintain the valveposition and withstand the ventricular force during ventricularcontraction or systole. Accordingly, the atrial cuff/collar hassufficient structural integrity to provide the necessary tension againstthe tethers without being dislodged and pulled into the left ventricle.After a period of time, changes in the geometry of the heart and/orfibrous adhesion between prosthesis and surrounding cardiac tissues mayassist or replace the function of the ventricular tethers in resistinglongitudinal forces on the valve prosthesis during ventricularcontraction.

Stent Structure

Preferably, superelastic metal wire, such as Nitinol® wire, is used forthe stent, for the inner wire-based leaflet assembly that is disposedwithin the stent, and for the sealing cuff wire form. As stated, it iscontemplated as within the scope of the invention to optionally useother shape memory alloys such as Cu—Zn—Al—Ni alloys, and Cu—Al—Nialloys. It is contemplated that the stent may be constructed as abraided stent or as a laser cut stent. Such stents are available fromany number of commercial manufacturers, such as Pulse Systems. Laser cutstents are preferably made from Nickel-Titanium (Nitinol®), but alsowithout limitation made from stainless steel, cobalt chromium, titanium,and other functionally equivalent metals and alloys, or Pulse Systemsbraided stent that is shape-set by heat treating on a fixture ormandrel.

One key aspect of the stent design is that it be compressible and whenreleased have the stated property that it return to its original(uncompressed) shape. This requirement limits the potential materialselections to metals and plastics that have shape memory properties.With regards to metals, Nitinol has been found to be especially usefulsince it can be processed to be austhenitic, martensitic or superelastic. Martensitic and super elastic alloys can be processed todemonstrate the required compression features.

In one preferred embodiment, the valve, in lateral cross-section, is“D-shaped”. Having one side that is relatively flat allows the valve toseat against the native anterior leaflet, tracking the shape of theanterior annulus, without putting excessive pressure on the aortic valvewhich is located immediately adjacent the anterior leaflet. The D-shapealso provides the rounded posterior valve/stent wall to track the shapeof the posterior annulus and seat securely against the posteriorleaflet.

In this regard, in one preferred aspect the deployment of the D-shapedvalve may be offset such that the flat wall, or straight line of the“D”, is positioned along the axis between the mitral annulus and theaortic valve.

In another preferred embodiment, the valve, in lateral cross-section, is“kidney shaped” or “kidney bean shaped”. This three-dimensional shape,like the D-shape, allows the valve to seat against the native anteriorleaflet, tracking the shape of the anterior annulus, without puttingexcessive pressure on the aortic valve which is located immediatelyadjacent the anterior leaflet.

Laser Cut Stent

One possible construction of the stent envisions the laser cutting of athin, isodiametric Nitinol tube. The laser cuts form regular cutouts inthe thin Nitinol® tube. Secondarily the tube is placed on a mold of thedesired shape, heated to the Martensitic temperature and quenched. Thetreatment of the stent in this manner will form a stent or stent/sealingcuff that has shape memory properties and will readily revert to thememory shape at the calibrated temperature.

Braided Wire Stent

A stent can be constructed utilizing simple braiding techniques. Using aNitinol wire—for example a 0.012″ wire—and a simple braiding fixture,the wire is wound on the braiding fixture in a simple over/underbraiding pattern until an isodiametric tube is formed from a singlewire. The two loose ends of the wire are coupled using a stainless steelor Nitinol coupling tube into which the loose ends are placed andcrimped. Angular braids of approximately 60 degrees have been found tobe particularly useful. Secondarily, the braided stent is placed on ashaping fixture and placed in a muffle furnace at a specifiedtemperature to set the stent to the desired shape and to develop themartensitic or super elastic properties desired.

The stent as envisioned in one preferred embodiment is designed suchthat the ventricular aspect of the stent comes to 1-5 points onto whichone or more anchoring sutures are affixed. The anchoring sutures(tethers) will traverse the ventricle and ultimately be anchored to theepicardial surface of the heart approximately at the level of the apex.The tethers when installed under slight tension will serve to hold thevalve in place, i.e. inhibit paravalvular leakage during systole.

Narrow Gauge Stent to Treat Commissural Regurgitation and/or SecondaryMitral Regurgitation

“Primary MR” is a term describing mitral regurgitation caused by ananatomic defect in the valve or associated tissue, such as the chordae.The defect can either be congenital or degenerative, with causal factorsranging from marfan syndrome to drug- or radiation-inducement.

“Secondary MR” (also known as “Functional MR”), unlike Primary MR, isclassified as a defect in valvular function or mechanics, as opposed toan anatomical defect. In such cases, an anatomically normal mitral valvehas become regurgitant, usually as a result of impaired left ventriclefrom dilated cardiomyopathy or a myocardial infarction. Causality can beeither ischemic or nonischemic. Specifically, chordae tendinae andpapillary muscles can be stretched from increased tension, and the valveannulus itself may become distended due to the altered position ofsurrounding myocardium. Frequently, dilation of the left ventricleresults in “volume overload” of blood during periods of systole,inhibiting full coaptation of the leaflets.

Secondary MR involves a defect in valvular function or mechanics, asopposed to an anatomical defect. In these cases, an anatomically normalmitral valve has become regurgitant, usually as a result of impairedleft ventricle from dilated cardiomyopathy or a myocardial infarction.Specifically, chordae tendinae and papillary muscles can be stretchedfrom increased tension, and the valve annulus itself may becomedistended due to the altered position of surrounding myocardium.Frequently, dilation of the left ventricle results in volume overloadduring periods of systole, inhibiting full coaptation of the leaflets.

Types of treatment currently in use for Secondary MR include treatmentsto decrease the circumference of the valvular orifice; decreasing thesize of the mitral orifice, either by cinching the leaflets orrestricting the movement of the leaflets; or remodeling the leftventricle to decrease the dimensions there. Examples of procedures tolimit the size of the mitral orifice and/or enhance leaflet coaptationinclude the anchoring of one or more balloon devices across the mitralvalve orifice to provide a backstop for leaflet coaptation and the useof sutures or clips to attach the leaflets at the point of coaptation.These methods are known to involve thrombotic and stenoticcomplications.

Secondary MR can be subclassified by leaflet movement (Carpentier'sclassification): type I (normal valve movement, such as annulardilatation or leaflet perforation); type II (excessive movement); andtype III (restrictive movement: Ma-diastolic restriction such asrheumatic disease; Mb-systolic restriction as in functional disease).

One particular aspect of secondary or “functional” mitral regurgitationis the presence of a “central jet” of regurgitant blood flowing throughand near the center of the point of coaptation during regurgitation.

In one non-limiting preferred embodiment, the prosthetic valve is usedto close the valve to this central jet flow, while leaving thecommissures free to seal. This embodiment has yielded unexpectedbenefits in ameliorating the effects of commissural regurgitation and/orsecondary mitral regurgitation, such as LV hypertrophy. It is thoughtthat this unexpected benefit is likely due benefit is potentially due tothe overall reduction in regurgitation and increased pumping efficiency,combined with the lessened deformity of the native commissures, thiseliminating most or all of the mitral commissural regurgitation.

In another non-limiting preferred embodiment, the diameter of the stentbody should be less than the diameter of the native mitral annulus. Inone preferred embodiment, the stent diameter is between 50% and 95% ofthe diameter of the native mitral annulus. In another preferredembodiment, the stent diameter is between 75% and 90% of the diameter ofthe native mitral annulus. Preferably, the valve is positioned withinthe point of coaptation so as not to impair the opening of either theposterior or anterior commissions, thereby allowing the prosthetic valveto stop central jet regurgitation, while avoiding structural deformationor interaction with the mitral commissures.

In another non-limiting preferred embodiment, the diameter of the stentbody should be less than the distance between the inward-facing tips ofthe two commissural cusps.

In another non-limiting preferred embodiment, the diameter of the stentbody should approximately match the distance between the inward-facingtips of the two commissural cusps. In another non-limiting preferredembodiment, the diameter of the stent body should be approximately 18-32mm. In a more preferred embodiment, the diameter of the stent bodyshould be 20-30 mm. In a more preferred embodiment, the diameter of thestent body should be 23-28 mm.

The average area of an open mitral valve is between 4 cm2 and 6 cm2. Inanother non-limiting preferred embodiment, the diameter of the stentbody may be between 75% and 99% of the mitral valve cross-sectionalleaflet diameter. In another preferred embodiment, the diameter of thestent body may be between 85% and 98% of the mitral valvecross-sectional leaflet diameter. In another preferred embodiment, thediameter of the stent body may be between 92% and 97% of the mitralvalve cross-sectional leaflet diameter.

The degree of severity of mitral regurgitation can be quantified by theregurgitant fraction, which is the percentage of the left ventricularstroke volume that regurgitates into the left atrium.

${{{Regurgitant}\mspace{14mu}{fraction}} = {\frac{V_{mitral} - V_{aortic}}{V_{mitral}} \times 100\%}},$

where V_(mitral) and V_(aortic) are respectively the volumes of bloodthat flow forward through the mitral valve and aortic valve during acardiac cycle. Methods that have been used to assess the regurgitantfraction in mitral regurgitation include echocardiography, cardiaccatheterization, fast CT scan, and cardiac MRI.

The degree of mitral regurgitation is often gauged according to theregurgitant fraction.

Determination of the degree of mitral regurgitation

Regurgitant Regurgitant Degree of mitral regurgitation fraction Orificearea Mild mitral regurgitation <20 percent Moderate mitral regurgitation20-40 percent   Moderate to severe mitral regurgitation 40-60 percent  Severe mitral regurgitation >60 percent >0.4 cm²

In another non-limiting preferred embodiment, the stent body shall beshaped to allow for continued commissural regurgitation of 20% or less.In a more preferred embodiment, the stent body shall be shaped to avoidcommissural deformation and/or commissural regurgitation of 10% or less.In another preferred embodiment, the stent body shall be shaped to avoidcommissural deformation and/or commissural regurgitation of 5% or less.

Leaflet and Assembly Structure

The valve leaflets are held by, or within, a leaflet assembly. In onepreferred embodiment of the invention, the leaflet assembly comprises aleaflet wire support structure to which the leaflets are attached andthe entire leaflet assembly is housed within the stent body. In thisembodiment, the assembly is constructed of wire and stabilized tissue toform a suitable platform for attaching the leaflets. In this aspect, thewire and stabilized tissue allow for the leaflet structure to becompressed when the prosthetic valve is compressed within the deploymentcatheter, and to spring open into the proper functional shape when theprosthetic valve is opened during deployment. In this embodiment, theleaflet assembly may optionally be attached to and housed within aseparate cylindrical liner made of stabilized tissue or material, andthe liner is then attached to line the interior of the stent body.

In this embodiment, the leaflet wire support structure is constructed tohave a collapsible/expandable geometry. In a preferred embodiment, thestructure is a single piece of wire. The wireform is, in one embodiment,constructed from a shape memory alloy such as Nitinol. The structure mayoptionally be made of a plurality of wires, including between 2 to 10wires. Further, the geometry of the wire form is without limitation, andmay optionally be a series of parabolic inverted collapsible arches tomimic the saddle-like shape of the native annulus when the leaflets areattached. Alternatively, it may optionally be constructed as collapsibleconcentric rings, or other similar geometric forms that are able tocollapse/compress which is followed by an expansion to its functionalshape. In certain preferred embodiments, there may be 2, 3 or 4 arches.In another embodiment, closed circular or ellipsoid structure designsare contemplated. In another embodiment, the wire form may be anumbrella-type structure, or other similar unfold-and-lock-open designs.A preferred embodiment utilizes super elastic Nitinol wire approximately0.015″ in diameter. In one preferred embodiment, the diameter is 0.012″.In this embodiment, the wire is wound around a shaping fixture in such amanner that 2-3 commissural posts are formed. The fixture containing thewrapped wire is placed in a muffle furnace at a pre-determinedtemperature to set the shape of the wire form and to impart it's superelastic properties. Secondarily, the loose ends of the wireform arejoined with a stainless steel or Nitinol tube and crimped to form acontinuous shape. In another preferred embodiment, the commissural postsof the wireform are adjoined at their tips by a circular connectingring, or halo, whose purpose is to minimize inward deflection of thepost(s).

In another preferred embodiment, the leaflet assembly is constructedsolely of stabilized tissue or other suitable material without aseparate wire support structure. The leaflet assembly in this embodimentis also disposed within the lumen of the stent and is attached to thestent to provide a sealed joint between the leaflet assembly and theinner wall of the stent. By definition, it is contemplated within thescope of the invention that any structure made from stabilized tissueand/or wire(s) related to supporting the leaflets within the stentconstitute a leaflet assembly.

In this embodiment, stabilized tissue or suitable material may alsooptionally be used as a liner for the inner wall of the stent and isconsidered part of the leaflet assembly.

Liner tissue or biocompatible material may be processed to have the sameor different mechanical qualities, e.g. thickness, durability, etc. fromthe leaflet tissue.

Deployment within the Valvular Annulus

The prosthetic heart valve is, in one embodiment, apically deliveredthrough the apex of the left ventricle of the heart using a cathetersystem. In one aspect of the apical delivery, the catheter systemaccesses the heart and pericardial space by intercostal delivery. Inanother delivery approach, the catheter system delivers the prostheticheart valve using either an antegrade or retrograde delivery approachusing a flexible catheter system, and without requiring the rigid tubesystem commonly used. In another embodiment, the catheter systemaccesses the heart via a trans-septal approach.

In one non-limiting preferred embodiment, the stent body extends intothe ventricle about to the edge of the open mitral valve leaflets(approximately 25% of the distance between the annulus and theventricular apex). The open native leaflets lay against the outsidestent wall and parallel to the long axis of the stent (i.e. the stentholds the native mitral valve open).

In one non-limiting preferred embodiment, the diameter shouldapproximately match the diameter of the mitral annulus. Optionally, thevalve may be positioned to sit in the mitral annulus at a slight angledirected away from the aortic valve such that it is not obstructing flowthrough the aortic valve. Optionally, the outflow portion (bottom) ofthe stent should not be too close to the lateral wall of the ventricleor papillary muscle as this position may interfere with flow through theprosthesis. As these options relate to the tricuspid, the position ofthe tricuspid valve may be very similar to that of the mitral valve.

In another embodiment, the prosthetic valve is sized and configured foruse in areas other than the mitral annulus, including, withoutlimitation, the tricuspid valve between the right atrium and rightventricle. Alternative embodiments may optionally include variations tothe sealing cuff structure to accommodate deployment to the pulmonaryvalve between the right ventricle and pulmonary artery, and the aorticvalve between the left ventricle and the aorta. In one embodiment, theprosthetic valve is optionally used as a venous backflow valve for thevenous system, including without limitation the vena cava, femoral,subclavian, pulmonary, hepatic, renal and cardiac. In this aspect, thesealing cuff feature is utilized to provide additional protectionagainst leaking.

Tethers

In one preferred embodiment, there are tethers attached to theprosthetic heart valve that extend to one or more tissue anchorlocations within the heart. In one preferred embodiment, the tethersextend downward through the left ventricle, exiting the left ventricleat the apex of the heart to be fastened on the epicardial surfaceoutside of the heart. Similar anchoring is contemplated herein as itregards the tricuspid, or other valve structure requiring a prosthetic.There may be from 1 to 8 tethers which are preferably attached to thestent.

In another preferred embodiment, the tethers may optionally be attachedto the sealing cuff to provide additional control over position,adjustment, and compliance. In this preferred embodiment, one or moretethers are optionally attached to the sealing cuff, in addition to, oroptionally, in place of, the tethers attached to the stent. By attachingto the sealing cuff and/or the stent, an even higher degree of controlover positioning, adjustment, and compliance is provided to the operatorduring deployment.

During deployment, the operator is able to adjust or customize thetethers to the correct length for a particular patient's anatomy. Thetethers also allow the operator to tighten the sealing cuff onto thetissue around the valvular annulus by pulling the tethers, which createsa leak-free seal.

In another preferred embodiment, the tethers are optionally anchored toother tissue locations depending on the particular application of theprosthetic heart valve. In the case of a mitral valve, or the tricuspidvalve, there are optionally one or more tethers anchored to one or bothpapillary muscles, septum, and/or ventricular wall.

The tethers, in conjunction with the sealing cuff or collar, provide fora compliant valve which has heretofore not been available. The tethersare made from surgical-grade materials such as biocompatible polymersuture material. Examples of such material include 2-0 exPFTE(polytetrafluoroethylene) or 2-0 polypropylene. In one embodiment thetethers are inelastic. It is also contemplated that one or more of thetethers may optionally be elastic to provide an even further degree ofcompliance of the valve during the cardiac cycle. Upon being drawn toand through the apex of the heart, the tethers may be fastened by asuitable mechanism such as tying off to a pledget or similar adjustablebutton-type anchoring device to inhibit retraction of the tether backinto the ventricle. It is also contemplated that the tethers might bebioresorbable/bioabsorbable and thereby provide temporary fixation untilother types of fixation take hold such a biological fibrous adhesionbetween the tissues and prosthesis and/or radial compression from areduction in the degree of heart chamber dilation.

Further, it is contemplated that the prosthetic heart valve mayoptionally be deployed with a combination of installation tethers andpermanent tethers, attached to either the stent or sealing cuff, orboth, the installation tethers being removed after the valve issuccessfully deployed. It is also contemplated that combinations ofinelastic and elastic tethers may optionally be used for deployment andto provide structural and positional compliance of the valve during thecardiac cycle.

Pledget

In one embodiment, to control the potential tearing of tissue at theapical entry point of the delivery system, a circular, semi-circular, ormulti-part pledget is employed. The pledget may be constructed from asemi-rigid material such as PFTE felt. Prior to puncturing of the apexby the delivery system, the felt is firmly attached to the heart suchthat the apex is centrally located. Secondarily, the delivery system isintroduced through the central area, or orifice as it may be, of thepledget. Positioned and attached in this manner, the pledget acts tocontrol any potential tearing at the apex.

Tines/Barbs

In another embodiment the valve can be seated within the valvularannulus through the use of tines or barbs. These may be used inconjunction with, or in place of one or more tethers. The tines or barbsare located to provide attachment to adjacent tissue. In one preferredembodiment, the tines are optionally circumferentially located aroundthe bend/transition area between the stent and the sealing cuff. Suchtines are forced into the annular tissue by mechanical means such asusing a balloon catheter. In one non-limiting embodiment, the tines mayoptionally be semi-circular hooks that upon expansion of the stent body,pierce, rotate into, and hold annular tissue securely.

Functions of the Spring Anchor

The spring anchor will form a spring-shaped wire or banded extendingfrom the base of the self-expanding stent. The anchor will providesupport to hold the stent within the natural valve annulus by beingcoiled around the chordae tendineae extending from the natural valveannulus. The spring mechanism of the anchor will allow consistentsupport to the prosthetic valve stent, despite repetitive deformation asthe chordae tendineae, valve annulus and surrounding tissue contract andrelease. The shape memory characteristics of the coil will allow eachloop deform and move independently in response to each heartcontraction, and then return to the original coil dimensions as theheart relaxes. The placement of the coil around the chordae tendineaewill anchor the stent to counteract the natural tendency of the stent tomove laterally with the cardiac tissue contractions and releases, andlongitundinally with the blood flow between the ventricle and theatrium.

Deployment of the Spring Anchor

The spring anchor will be fused to the prosthetic valve stent via eitherwelding, soldering or adhesion prior to insertion of the entire valveand anchor assembly into a delivery catheter.

The delivery catheter will approach the heart via either transvenous,transarterial or percutaneous delivery. Delivery may be made throughinto the left or right ventricle, or the left or right atrium.

Delivery into the right ventricle may be made through the intercostalspace and thereby through the lateral ventricular wall. Delivery intothe right atrium may be made using a transvenous approach.

Delivery into the left ventricle may be made through the intercostalspace, using an apical approach or through the lateral ventricular wall.A transarterial retrograde aortic valve approach and a transvenousseptostomy approach may also be used.

Upon deployment of the self-expanding prosthetic valve within the nativevalvular annulus, whether in the tricuspid valve annulus, mitral valveannulus, or otherwise, the catheter sheath will be withdrawn, allowingthe spring anchor to deploy. Such anchor deployment will result in theexpanding of the coiled loops into a spring-like shape of sufficientdiameter to allow circumnavigation of the chordae tendineae.

After release of the spring anchor, control of the anchor will bemaintained via surgical tools contained within the catheter and known inthe art to guide the anchor around the chordae tendineae in a rotating,screw-like motion. The number of rotations performed will be determinedby the number of loops contained within the spring anchor.

Alternatively, the surgeon may use a surgical tool contained within thecatheter and known in the art to secure and pull the chordae tendineaewithin the circumference of one or more loops of the anchor.

Upon securing the anchor around the chordae tendineae, surgical toolsmay or may not be used to secure one or more anchoring tethers tosurrounding pericardial tissue for additional support.

Upon the securing of the valve stent within the native annulus, thespring anchor around the chordae tendineae and the tethers, if any, tothe pericardial tissue, all surgical tools manipulating said componentswill be disengaged, pulled into the catheter and the catheter withdrawn.

Spring Anchor Structure

The spring anchor is a single wire or band of shape-memory material, forexample a 0.012″ Nitinol wire, formed into a series of two or morecircular loops, in which the proximal loop is attached to the base ofthe prosthetic valve stent.

Once the proximal loop has been attached to the base of theself-expanding stent, the additional loop(s) will radiate outwardaxially from the stent in the shape of a spring. The distal loop will beopen, allowing for the tip to be placed outside a chordae tendineaeduring deployment, then rotated about a plurality of chordae tendineaein either a clockwise or counterclockwise direction until eachnon-proximal loop is deployed about and anchored against the outertissue of the chordae tendineae.

In a preferred embodiment, the spring anchor is made of materialidentical to the material used to construct the base of the stent. Inanother preferred embodiment, the material of the anchor differs fromthe material of the stent base.

In a preferred embodiment, the proximal loop of the spring anchor iswelded to the base of the stent, forming a continuous joint around thefull diameter of the base. In another embodiment, the proximal loop ofthe anchor is soldered to the stent base, or adhered to the stent baseusing an adhesive substance known in the art.

Because of the shape-memory material's flexibility, the anchor has theability to articulate back and forth both laterally and longitudinally,while returning to its original shape formation after each deformation.The loops can independently move back and forth, and can spring back totheir original position due to the relative stiffness of the wire orband. The coil has a certain modulus of elasticity such that, whenattached to the wire of the stent, is able to allow the collar to move.This flexibility gives the anchor, upon being deployed within apatient's heart, the ability to conform to the anatomical shapenecessary for a particular application. In the example of a prostheticmitral valve, the anchor is able to conform to the irregularities in theshape and disposition of the chordae tendineae, and to provide a tightgrip against the chordae tendineae tissue to provide support to theprosthetic valve. As stated previously, this feature importantlyprovides a degree of flexibility in sizing the anchor and preventsdislocation of the anchor and/or prosthetic valve due to wear.

In one preferred anchor embodiment, each loop in the coil issubstantially uniform in shape and diameter. In another preferredembodiment of the present invention, the loops may be of varying shapesand sizes. In this example, it is contemplated that the loops maygradually increase in diameter as they extend away from the stent base.The size and pattern of the loops may vary based on whether the valvereplacement is being performed on the mitral valve or the tricuspidvalve.

The anchor form is constructed so as to provide sufficient structuralintegrity to withstand the intracardiac forces without dislocating,permanently deforming or fracturing. The anchor assembly is preferablyconstructed of a wire or band constructed of a shape memory alloy,polymer or ceramic, such as Nitinol®, that is capable of maintaining itsfunction as an anchor for the tubular stent while under lateral andlongitudinal forces that might cause a structural deformation or valvedisplacement. It is contemplated as within the scope of the invention tooptionally use other shape memory alloys or materials such as listedherein.

For example, assuming a mitral valve replacement prosthesis, the heartis known to generate an average left atrial pressure between about 8 and30 mm Hg (about 0.15 to 0.6 psi). This left atrial filling pressure isthe expected approximate pressure that would be exerted in the directionof the left ventricle when the prosthesis is open against the prosthesiswithin the mitral valve annulus. The anchor counteracts this downwardlongitudinal pressure against the prosthesis in the direction of theleft ventricle to keep the valve from being displaced or slipping intothe ventricle. In contrast, left ventricular systolic pressure, normallyabout 120 mm Hg, exerts a force on the closed prosthesis in thedirection of the left atrium. The anchor would also counteract thisforce and be used to maintain the valve position and withstand theventricular force during ventricular contraction or systole. Tethers mayalso be used to secure position against any other directional forces asnecessary. After a period of time, changes in the geometry of the heartand/or fibrous adhesion between prosthesis and surrounding cardiactissues, or between the anchor and surrounding cardiac tissues, mayassist or replace the function of anchor and/or the ventricular tethersin resisting longitudinal forces on the valve prosthesis duringventricular contraction.

Description of Surface Improvements Figures

Referring now to the FIGURES, FIG. 1 shows one embodiment of aprosthetic heart valve 110 according to the present invention,comprising tubular stent 112 having optional tether attachmentstructures 114 at one end and tubular stent 112 provides integratedsealing cuff 116 at the other end. Leaflet assembly 118 is disposedwithin stent 112 and supports valve leaflets 120. Sealing cuff 116 hasindependent articulating loops of wire 122 and interior liner/covering124 and exterior liner/covering 125.

Tubular stent 112 may be an expandable laser cut stent or an expandablebraided stent. Tubular stent 112 may be constructed of Martensitic orsuper elastic metal alloys. Tubular stent 112 may be compressed alongits longitudinal axis and will fit into a catheter-based stent deliverysystem. When the tubular stent 112 is delivered to the location where itis to be installed, it is expelled from the catheter by an obturator anddeposited at the site where it is to be deployed.

Tubular stent 112 includes a plurality of optional tether attachments114 upon which a tether (not shown) may be connected. FIG. 1 shows anembodiment having three tether attachments which are integrated into thedistal portion of the stent 112.

Leaflet assembly 118 is a separate but integrated structure that isdisposed within the stent 112. Leaflet assembly 118 functions to providethe structure upon which the valve leaflets or cusps 120 are located.Leaflet assembly 118 may be made entirely of stabilized tissue or it maybe a combination wire and tissue structure. Where leaflet assembly 118is composed entirely of tissue, it is contemplated that the leafletassembly, leaflet support structure, and leaflets or cusps 120 are madefrom tissue.

The prosthetic valve is covered with multiple layers of either syntheticmaterial, or tissue, or both. This feature is described in greaterdetail herein. Different qualities of stabilized tissue, i.e. thin orthick, structurally rigid or flexible as it may be, may be used for thedifferent components of the sealing cuff top covering 124, the stentinterior liner/covering 124, the leaflet assembly 118 and the leaflets120. Where leaflet assembly 118 is composed of wire and tissue, itcontemplated that assembly or support(s), or both, may be made fromwire, and the leaflet cusps 120 would necessarily be made from tissue.

Prosthetic heart valve 110 also includes sealing cuff 116. FIG. 1 showssealing cuff 116 formed from a sealing cuff wire form 122 that iscovered by, in one embodiment, interior liner/covering 124 and exteriorliner/covering 125. Hash marks are provided to illustrate how the stentwire/cuff wire is covered on both sides. Hash marks may also indicatethat the tissue or fabric is opaque, however it is not required. In oneembodiment, the sealing cuff wire form is an extension of the stentitself, where the stent has been heated and manipulated upon a form tocreate the extended spindles of the flat, collar plate of the sealingcuff.

Referring now to FIG. 2 is a cut-away sectional view of a multi-layertranscatheter valve according to one embodiment of the presentinvention. FIG. 2A shows a three-layer construction having syntheticpolymeric material 134 on the inside, a stent made from wire 132, e.g.Nitinol®, and an outer covering made from a synthetic polymeric material134, e.g. Dacron® polyester. FIG. 2B shows a three-layer constructionhaving specially treated tissue 130 on the inside, a stent made fromwire 132, e.g. Nitinol®, and an outer covering made from a syntheticpolymeric material 134, e.g. Dacron® polyester.

Referring now to FIG. 3, FIG. 3A illustrates an embodiment whereintissue 130 is interior, supporting stent 132, and having outer syntheticmaterial covering 134. FIG. 3B illustrates an embodiment whereinsynthetic material 134 is used in both the interior and the exterior,with the metal stent 132 sandwiched between them. FIG. 3C illustrateshow multiple layers may be constructed, with, for example, from insidethe lumen of the stent to the outside, a synthetic material 134 islayered with a treated tissue layer 132, which is attached to the stent130, which in turn is covered with a synthetic material 136 which may bethe same or different as the inner synthetic material 134.

Referring now to FIG. 4, FIG. 4A is an electron microscope image of anelectrospun PGA nanofiber fabricated to have a certain porosity anddensity. FIG. 4B is an electron microscope image of an electrospun PLGAnanofiber fabricated to have a different porosity and density. FIG. 4Cis an electron microscope image of an electrospun PLLA-CL nanofiberfabricated to have an alternative porosity and density. These types ofelectrospun fibers are contemplated for use as one of the preferred, butnot necessarily limited to, synthetic materials for use on thetranscatheter valve herein.

Referring now to FIGS. 5A-5D, there is an exploded view of oneembodiment of the parts of the invention. FIG. 5A shows cuff covering124 in a treated tissue example. In other alternative embodiments, thetissue may extend through the entirety of the lumen of the stent, ascompared to being used only on the cuff, as here. Both variations areincluded within the invention. FIG. 5B shows heat-formed stent 112 withcuff loops 122. FIG. 5C shows synthetic polymeric material 128 as a bandof material ready for covering the external/outer wall of the stent bodybelow the cuff. As with the tissue, the synthetic material may coverpart or all of the exterior of the stent, including the underside of thecuff loops. FIG. 5D shows a piece of treated tissue 120, without furtherdetail, for use as the valve leaflet structure.

Referring now to FIG. 6 is a cut-away view of a heart with a deliverycatheter containing a prosthetic heart valve according to the presentinvention and accessing the heart using an apical approach. It iscontemplated that other surgical approaches to the heart, and valves inaddition to the mitral valve, are within the scope of the inventivesubject matter claimed herein. FIG. 6 shows the delivery catheter 144advanced to through the mitral valve and into the left atrium fordeployment of the prosthetic valve 110.

Referring now to FIG. 7, FIG. 7 shows the lateral deployment of oneembodiment of a prosthetic valve according to the present invention andshows a prosthetic valve delivery catheter 144 that has accessed theleft atrium via the left ventricle by way of a lateral trans-ventricularwall approach through the lateral wall of the left ventricle of theheart.

Referring now to FIG. 8, FIG. 8 is a cut-away view of a heart with adelivery catheter 144 containing a prosthetic heart valve according tothe present invention and accessing the heart using an apical approachinto the right ventricle. It is contemplated that other surgicalapproaches to the heart, and valves in addition to the mitral valve, arewithin the scope of the inventive subject matter claimed herein. FIG. 8shows the delivery catheter 144 advanced to the tricuspid valve and intothe right atrium for deployment of the prosthetic valve 110.

FIGS. 9A-9D is a series of drawings of the deployment of one embodimentof a prosthetic valve according to the present invention. FIGS. 9A-9D isa series of views of the tip of one embodiment of a delivery catheteraccording to the present invention containing a pre-loaded prostheticvalve which is being pushed out of the delivery catheter, i.e. by anobturator, starting with (A) the valve completely within the catheter,(B) the sealing cuff portion being in view, (C) the stent bodyfollowing, and (D) the prosthetic valve with attached tethers forpositioning and/or adjustment and/or securing the valve to tissue. FIGS.9A-9D show how the prosthetic valve 110 is deployed from flexibledeployment catheter 144. FIG. 9B shows the sealing cuff 116 emergingfrom the catheter 144. FIG. 9C shows the sealing cuff 116 and stent 112partially expelled from the delivery catheter 144. FIG. 9D shows theprosthetic valve completely expelled from the delivery catheter 144 withtethers 138 attached to the stent body and trailing behind into thecatheter. FIG. 9D further shows tethers 138 attached to the stent 112,with prosthetic valve 110 now expanded and delivered (but not positionedor adjusted), as the delivery catheter 144 is withdrawn away from thetarget location, e.g. atrium.

Referring now to FIG. 10, FIG. 10 shows a depiction of a fully deployedprosthetic heart valve 110 installed in the left mitral valve of theheart having the tethers 138 attached to the left ventricle apex of theheart. Tethers 138 in this embodiment extend through the heart muscleand are attached to securing device 140, here shown as a pledget placedon the epicardial surface and having tethers fastened thereto. In thisembodiment, the pledget 140 performs the function of an anchor to whichthe tethers 138 are attached. Tethers 138 are strung through the leftventricle apex and pulled downward to seat prosthetic valve 110 in theatrial valve area. The completely installed prosthetic valve is held inthe left atrium by the sealing cuff 116 and secured to the apex of theheart by tethers 138. The tethers may be held in place by a securingdevice which in this aspect of the invention is a pledget 140 that thetethers are threaded through and secured against, i.e. by tying a knotor using a cinching feature.

Referring now to FIG. 11, FIG. 11 is a detailed cross-sectional view (ofthe heart) of one embodiment of a prosthetic heart valve according tothe present invention deployed within the mitral valve aperture of theheart and anchored, in an alternative embodiment, between (A) where itis seated or lodged by the atrial sealing cuff and (B) the ventriculartethers connected to papillary muscles 166 and/or ventricular walland/or tether(s) attached to septum 164, which are each secured by oneor more securing tissue anchors, anchoring devices, or anchoringmethods.

Description of Shuttlecock Annular Valve Figures

Referring now to the FIGURES, FIG. 12 shows one embodiment of aprosthetic heart valve 110 according to the present invention,comprising tubular stent 112 having tether attachment structures 138 andcollar 116. Leaflet assembly 118 is disposed within stent 112 andsupports leaflets 120 (also not shown).

As stated, tubular stent 112 may be an expandable laser cut stent or anexpandable braided stent. Tubular stent 112 may be constructed ofMartensitic or super elastic metal alloys. Tubular stent 112 may becompressed in diameter along its longitudinal axis and will fit into acatheter-based stent delivery system. When the tubular stent 112 isdelivered to the location where it is to be installed, it is expelledfrom the catheter by an obturator and deposited at the site where it isto be deployed.

Tubular stent 112 may include a plurality of tether attachments (notpictured) to which a plurality of tethers 138 may be connected. FIG. 12shows an embodiment having four tether attachments which are integratedinto the distal portion of the stent 112, four leading to an pericardialattachment point at the apex of the left ventricle, where the aresecured to securing device/pledget 140.

Leaflet assembly 118 is a separate but integrated structure that isdisposed within the stent 112. Leaflet assembly 118 functions to providethe structure upon which the valve leaflets or cusps 120 are located.Leaflet assembly 118 may be made entirely of stabilized tissue or it maybe a combination wire and tissue structure. Where leaflet assembly 118is composed entirely of tissue, it is contemplated that the leafletassembly, leaflet support structure, and leaflets or cusps 120 are madefrom tissue. It is contemplated as within the scope of the inventionthat different qualities of stabilized tissue, i.e. thin or thick,structurally rigid or flexible as it may be, may be used for thedifferent components of the collar covering 124, the stent covering, theleaflet assembly 118 and the leaflets 120. Where leaflet assembly 118 iscomposed of wire and tissue, it contemplated that assembly orsupport(s), or both, may be made from wire, and the cusps 120 wouldnecessarily be made from tissue.

Prosthetic heart valve 110 also includes collar 116. FIG. 12 showscollar 116 originating at or near the base of the stent body andexpanding in diameter within the native valve annulus away from thedistal end (ventricular) of the stent body toward the proximal (atrial)end of the stent body.

As stated, collar 116 may be a band of metal tape, a wire structure,made from flexible synthetic material, or made from tissue material, andmay be a separate attached structure, or may be constructed as anintegral part of the stent body when the stent body is manufactured.Annular tissue is seen exerting lateral pressure onto collar 116. In oneembodiment, the collar is an extension of the stent itself, where thestent has been heated and manipulated upon a form to create the extendedflat, inverted plate of the collar. In another embodiment, the collar ismade separate from the stent 112 and attached as a flat plateconstructed to include an inner rim 146 and an outer rim 148, with joint142 where the collar 116 meets the tubular stent 112.

Referring now to FIGS. 13A-13B, FIG. 13A is a side view illustrationshowing stent 112, collar 116 and joint 130 located at the distal end ofthe stent body 116. FIG. 13B is a side view illustration showing analternate embodiment of stent 112, collar 116 and joint 130 attachedfurther up stent body away from the distal end of the stent body 116.

Referring to the stent body, it is contemplated as within the scope ofthe invention to include both laser cut stent technology and/or thebraided stent technology. Where the collar is an extension of a braidedstent and forms a unitary stent-collar construction, the collar isformed by heating a Nitinol™ stent on a mold to create the properextension and angle necessary to establish the collar or collar portion.

Where the stent is laser cut, the collar may be manufactured as aunitary laser-cut stent-collar construction. In this embodiment, thecollar wire form and the stent are laser cut within the same overallmanufacturing process. Where the collar wire form is made separate fromthe stent and attached as a flat collar plate, the collar and stent maybe manufactured/laser cut separately and attached using laser weld orother similar technique to create a non-fatiguing elastic stent-collarjoint capable of maintaining elastic compliance while it is deployed.

As noted, the rim or joint may consist of an artificial transition pointbetween the stent and the collar where the stent has been heated tochange the shape and angle of the stent or has been laser cut to createit's overall form, or the rim may consist of a constructed transitionpoint such as a laser welded joint for attaching two component parts.

Referring now to FIGS. 14A-14C, FIG. 14A shows an embodiment of theinvention, and in particular, the valve leaflets, whereby a prostheticmitral valve is supplied. FIG. 14B shows an embodiment of a bicuspidmitral valve made from tissue in the shape a hyperbolic paraboloid, orsaddle. This specific shape, for the prosthetic mitral valve, mimics thenative valve, and takes into consideration the anterior to posteriorcompression or deformation that occurs due to adjacent cardiovasculartissues, and takes into consideration the lower, commissural portionssimilar to the native valve. Since the inventive collar is flexible anddeformable, this allows proper alignment of the valve leaflets withinthe stent body, greatly enhancing functionality. FIG. 14C illustrateshow a tricuspid valve may also be used within the scope of the presentinventive subject matter.

Referring now to FIG. 15, the collar has the ability to travel or flexin and out, along the lateral axis; longitudinal defined by thelengthwise axis of the stent. As stated, this flexibility or complianceprovides the prosthetic heart valve, specifically the collar, upon beingdeployed within a patient's heart, the ability to conform to theanatomical shape of the native annulus, maintain the conforming shapeduring the cardiac cycle, and provide a tight seal against the atrialtissue adjacent the mitral valve aperture. This feature reduces orremoves the guesswork that often accompanies the pre-surgical sizing ofa mitral valve. By providing a better fit, this necessarily preventsblood from leaking around the implanted prosthetic heart valve.

FIG. 15 shows how the prosthetic valve 110 may be fitted with a tissuecovering 126 that is thin, durable, and may be attached to the stentbody 116. FIG. 15 also shows how the collar 116 may consist in oneembodiment as a two-part structure consisting of flexible member 152 andsupport structure 150. Circular support structure 140 may be made as adisc or halo or series of loops from the stent itself by heat-forming orby laser-cutting, or may be an independent structure that is laterattached or welded. In this embodiment, flexible member may be made froma synthetic material such as an elastic polymer fabric like a surgicalpolyester-linked fabric known in the art. Support structure 150 may becovered with thin tissue 126 such as for example, in a non-limitingpreferred embodiment, a 0.005 inch thick tissue made according to theprocesses disclosed herein. Leaflet cusp 120, here shown internal to thestent 112, may be made of the same tissue material as tissue covering126. In certain embodiments, leaflet tissue may be processed to providea thicker or thinner tissue as may demanded by a particular deployment.For example, very thin tissue would be useful where the prosthetic valveis being deployed in a peripheral or non-cardiac vasculature and needsto be very small. In another embodiment, the leaflet tissue may beselected to be thicker to add stability or wear or function, for aparticular use.

The prosthetic valve may be sized according to the patient'scardiovascular needs. Smaller patients may need smaller devices. Varyingheart anatomies may call for specific sizes also, depending on thepathology presented. In a preferred embodiment, the pericardial stentbody is about 28 mm in diameter with support structure 150 extending toabout 45 mm in diameter. It is contemplated as within the scope of theinvention that the stent body diameter may range from about 2 mm indiameter to about 30 mm in diameter. It is contemplated that the supportstructure 150 may extend beyond the diameter of the stent body from 0.1mm to about 20.0 mm, depending on use.

The height may be in one preferred embodiment about 5 mm-15 mm in totalbody length. It is contemplated as within the scope of the inventionthat the height range of the prosthetic valve length may range fromabout 2 mm to about 30 mm in total body length. The tethers may comprisefrom 1 to about 96 tethers securing the prosthetic valve in place. Inone embodiment, there may be a plurality of tethers 138 integrated withthe stent body.

Stent 112 may include a liner contemplated as being made of tissue orbiocompatible material as disclosed herein. The stent liner may be aninner stent liner and/or an outer (surface) stent liner.

Referring now to FIG. 16, an alternate preferred embodiment isillustrated showing stent body 112 covered with treated thin tissue 126,collar 116 made from a polyester or polyester-type fabric mesh whichspans from support structure 140 to the distal end of the stent body112. Support structure 140 is also covered with thin (e.g. 0.005″, 0.127mm) tissue 126. Multiple tethers 114 are shown attached to tether posts144, and anchored to cardiac tissue as well as an elongated tether 138connected apically to a pericardial pledget 146. Saddle shaped bicuspidleaflet 118 is shown disposed within stent body 112.

Referring now to FIG. 17 is a cut-away view of a heart with a deliverycatheter containing a prosthetic heart valve according to the presentinvention and accessing the heart using an apical approach. It iscontemplated that other surgical approaches to the heart, and valves inaddition to the mitral valve, are within the scope of the inventivesubject matter claimed herein. FIG. 17 shows the delivery catheter 144advanced to through the mitral valve and into the left atrium fordeployment of the prosthetic valve 110.

Referring now to FIG. 18, FIG. 18 shows the lateral deployment of oneembodiment of a prosthetic valve according to the present invention andshows a prosthetic valve delivery catheter that has accessed the leftatrium via the left ventricle by way of a lateral trans-ventricular wallapproach through the lateral wall of the left ventricle of the heart.FIG. 18 shows a prosthetic valve delivery catheter 144 that has accessedthe left atrium via the left ventricle by way of a lateraltrans-ventricular wall approach through the lateral wall of the leftventricle of the heart for deployment of the prosthetic valve 110.

Referring now to FIG. 19 is a cut-away view of a heart with a deliverycatheter containing a prosthetic heart valve according to the presentinvention and accessing the heart using an apical approach into theright ventricle. It is contemplated that other surgical approaches tothe heart including, and without being limited to, are femoral arteryaccess, axillary artery access, brachial artery access, radial arteryaccess, intrathoracic/pericardial, and other access methods. It is alsocontemplated that valves in addition to the mitral valve, are within thescope of the inventive subject matter claimed herein, such as forinstance the tricuspid and the aortic. FIG. 19 shows the deliverycatheter 144 advanced to the tricuspid valve and into the right atriumfor deployment of the prosthetic valve 110.

Referring now to FIGS. 20A-20D, FIG. 20A is a D-shaped embodiment of aprosthetic valve according to the present invention. FIG. 20A showsstent 112 having collar 116 and mitral leaflets 120. Mitral leaflets 120are shown at or near the top of stent 112 providing a mechanism foravoiding LVOT as described earlier. FIG. 20B shows another D-shapedembodiment of a prosthetic valve according to the present invention.FIG. 20B shows flexible member 152 covering stent 112 and spanningbetween stent 112 and support structure 150. Flexible member 152 andsupport structure 150 together comprise an alternative preferredembodiment of a collar 116. Support structure 150 is shown as a borderof loops. As previously described, support structure may be formeddirectly out of the stent material, laser cut from a unitary piece ofNitinol®, or attached separately. Support structure 150 is shown here inthis example without a layer of tissue or fabric, but it may also becovered as such. Again, mitral leaflets 120 are shown at or near the topof stent 112 providing a mechanism for avoiding LVOT as describedearlier. FIG. 20C is an illustration of a kidney or kidney-bean shapedembodiment of a prosthetic valve according to the present invention.FIG. 20C shows flexible member 152 covering stent 112 and spanningbetween stent 112 and support structure 150. Flexible member 152 andsupport structure 150 together comprise an alternative preferredembodiment of a collar 116. Support structure 150 is shown as a borderof loops. FIG. 20D is a cross-sectional view of an embodiment of aprosthetic valve according to the present invention. FIG. 20D showsleaflets 120 disposed within the lumen formed by stent walls 112.Support structure 140 is shown formed from and an integral piece ofstent 112. Flexible member 152 is seen spanning between the distal endof stent 112 and the proximal end of support structure 150. Supportstructure 150 is shown covered by stabilized tissue 126.

Description of Spring Anchor Figures

Referring now to the FIGURES, FIG. 21 is a perspective view illustrationevidencing one embodiment of a prosthetic heart valve 110 according tothe present invention, comprising tubular stent 112 having spring anchorattachment 156 attached to stent base 154. Leaflet assembly 118 isdisposed within stent 112.

As stated, tubular stent 112 may be an expandable laser cut stent or anexpandable braided stent. Tubular stent 112 may be constructed ofMartensitic or super elastic metal alloys. Tubular stent 112 may becompressed in diameter along its longitudinal axis and will fit into acatheter-based stent delivery system. When the tubular stent 112 isdelivered to the location where it is to be installed, it is expelledfrom the catheter by an obturator and deposited at the site where it isto be deployed.

Tubular stent 112 includes spring anchor attachment 156. FIG. 21 showsan embodiment having the spring anchor attachments wherein the proximalloop of the coil is attached to the stent base 154, and the non-proximalloops extend out from such base in a spring shape.

Referring now to FIG. 22, FIG. 22 is a perspective view illustrationshowing stent 112 seated within a native mitral valve annulus withleaflet assembly 118 disposed within stent 112. Stent base 154 appearsbeneath the native annulus and within the chordae tendineae, where it isfused to the proximal loop of spring anchor 158. Spring Anchor 156extends outward from its proximal loop and each non-proximal loopencircles the chordae tendineae.

As noted, the stent base 154 may comprise an artificial transition pointbetween the stent and the spring anchor proximal loop 158, whichtransition point may consist of a welded attachment, a solderedattachment, or an adhesive attachment.

As previously discussed, spring anchor 156 has the ability to travel orflex both in and out, and up and down, as required by the movements inthe cardiac tissue associated with heart contraction, while moving backinto its natural spring-like shape with each heart muscle relaxation. Asstated, the pliability of anchor 156 provides the prosthetic heartvalve, upon deployment within a patient's heart, with added stabilitywithin the native annulus, enhancing the ability of stent 112 to bothmaintain a conforming shape during the cardiac cycle, and provide atight seal against the atrial tissue adjacent the mitral valve aperture.By providing an anchor with characteristics to stent 112, the potentialfor blood leakage around the implanted prosthetic heart valve isminimized, as is the potential for the stent to dislodge into either theventricle or atrium, resulting in catastrophic failure.

Referring now to FIGS. 23A-23C, FIG. 23A shows an embodiment of theinvention, and in particular, the valve leaflets, whereby a prostheticmitral valve is supplied. FIG. 23B shows an embodiment of a bicuspidmitral valve made from tissue in the shape a hyperbolic paraboloid, orsaddle. This specific shape, for the prosthetic mitral valve, mimics thenative valve, and takes into consideration the anterior to posteriorcompression or deformation that occurs due to adjacent cardiovasculartissues, and takes into consideration the lower, commissural portionssimilar to the native valve. Since the inventive collar is flexible anddeformable, this allows proper alignment of the valve leaflets withinthe stent body, greatly enhancing functionality. FIG. 23C illustrateshow a tricuspid valve may also be used within the scope of the presentinventive subject matter.

Referring now to FIG. 24, stent 112 is again seated within a nativemitral valve annulus, here seen in cross-section, with valve leafletassembly 118 disposed within stent 112. In addition, mesh collar 116 hasbeen attached to the proximal end of stent 112 for additional stabilityabove the native annulus. Stent base 154 is fused to the spring anchorproximal loop 158, while the non-proximal loops of spring anchor 156extend downward through the ventricle and around the chordae tendineae(not shown here). In addition, tethers 138 are attached to the fusedstent base 158/spring anchor proximal loop 154, and extend outward inmultiple directions where they are anchored into surrounding nativetissue. Several of tethers 138 are extended to the apex of the leftventricle for attachment to and through a pledget 140 on the pericardialsurface. Tethers 138 and spring anchor 156 may be used separately or inconjunction to provide stabilization to stent 112.

Referring now to FIG. 25, FIG. 25 is a cut-away view of a heart with adelivery catheter containing a prosthetic heart valve with attachedspring anchor according to the present invention and accessing the heartusing an apical approach. It is contemplated that other surgicalapproaches to the heart, and valves in addition to the mitral valve, arewithin the scope of the inventive subject matter claimed herein. FIG. 25shows the delivery catheter 144 advanced to through the mitral valve andinto the left atrium for deployment of the prosthetic valve 110 andattached spring anchor 156, and rotating to encircle the spring-shapedspring anchor 156 around the chordae tendineae (not shown).

Referring now to FIG. 26, FIG. 26 shows the lateral deployment of oneembodiment of a prosthetic valve 110 prior to release of spring anchor156 (not shown) according to the present invention and shows aprosthetic valve delivery catheter 144 that has accessed the left atriumvia the left ventricle by way of a lateral trans-ventricular wallapproach through the lateral wall of the left ventricle of the heart.FIG. 26 shows a prosthetic valve delivery catheter 144 that has accessedthe left atrium via the left ventricle by way of a lateraltrans-ventricular wall approach through the lateral wall of the leftventricle of the heart.

Referring now to FIG. 27, FIG. 27 is a cut-away view of a heart with adelivery catheter 144 containing a prosthetic heart valve 110 accordingto the present invention and accessing the heart using an apicalapproach into the right ventricle. It is contemplated that othersurgical approaches to the heart, and valves in addition to the mitralvalve, are within the scope of the inventive subject matter claimedherein. FIG. 27 shows the delivery catheter 144 advanced to thetricuspid valve and into the right atrium for deployment of theprosthetic valve 110, prior to release of spring anchor 156 (not shown).

Description of Annular Clamps Figures

FIG. 28A shows a perspective view of a wire stent 112 with fourclamp-style annulus anchoring members 160 located around the outside.FIG. 28B shows a side view of the same wire stent 112 with fourclamp-style annulus anchoring members 160.

FIG. 29 shows a side view of a closed clamp-style annulus anchoringmember 160.

FIG. 30A show a perspective view of a clamp-style annulus anchoringmember 160 in the open position, comprising the following parts: pin162, spring 168, two interdigitated middle members 170, two pairs ofsemicircular fingers 172, each with a tapered point 174. FIG. 30B showsa perspective view of the same clamp shown in FIG. 30A, but in theclosed position with the ends of the semicircular fingers 172interdigitated.

FIG. 31A shows a side view of the clamp-style annulus anchoring member160 shown in FIG. 30A, but with a pressure-bearing member 176 attachedto the flange portion of each middle member 170 via the hole centered insuch flange (not shown), and exerting pressure to hold the clamp open.The pressure bearing members 176 are emanating from a catheter 144 in astraight position, exerting outward pressure on the clamp to hold itopen. FIG. 31B shows a partially exploded view of the clamp and pressurebearing members 176, evidencing the holes 178 centered in the middlemember flanges and the attachment stud 180 of each pressure bearingmember. The figure shows the moment of release as the crimped point ofthe pressure bearing members 176 extend from catheter 144 and cause thepressure bearing members to release from the middle members 170 of theclamp, thereby allowing the torque of spring 168 (not shown) to snap theclamp shut.

FIG. 32A shows a perspective view of a single semicircular finger 172,with a slot 182 along the outer ridge and a series of triangularprotrusions 184 along one side for interlocking with another finger ofthe same design. FIG. 32A also evidences a tip barb 186 above taperedpoint 174, for securing the clamp into native tissue. FIG. 32B shows aside view of the same semicircular finger pictured in FIG. 32A.

FIG. 33A shows a perspective view of the outer and distal side of thecenter portion component of a middle member of the clamp assembly shownin FIG. 30A, with machine tooling slots 188 and a ridged lockingmechanism 190 for interlocking with other components of the clampassembly, as well as stud attachment 192. FIG. 33B shows a perspectiveview of the inner and distal side of the same center portion componentpictured in FIG. 33A.

FIG. 34A shows a perspective view of a clamp assembly in the openposition, comprising a set of four closing members 174, each with a holebored directly into its proximal end through which a pin 162 has beenthreaded, with the closing members 174 interdigitated such that thefirst and third closing members close in one direction while the secondand fourth closing members close in the opposite direction. Each closingmember has a tapered distal tip 174. FIG. 34B shows the same assembly asFIG. 34A, but in the closed position.

FIG. 35A shows a side perspective of a clamp assembly in the openposition, comprising a set of four closing members 170, each with a holebored directly into its proximal end through which a pin 162 has beenthreaded, with the closing members 170 interdigitated such that thefirst and third closing members close in one direction while the secondand fourth closing members close in the opposite direction. Each closingmember has a tapered distal tip 174 with a barb feature 186. FIG. 35Bshows the same assembly as FIG. 34A, from an angled perspective.

FIG. 36A shows a side view of the clamp assembly of FIG. 35A, but in aclosed position. FIG. 36B shows the same assembly as FIG. 36A, but froman angled perspective.

FIGS. 37A-37F show a variety of possible dimensions of variouscomponents of a clamp assembly.

FIG. 38 shows a wire stent 112 with an integrated cuff 116 comprisingstud assemblies 192 for a suction fin and glue fin.

FIG. 39 shows a cross-section of the integrated cuff 116 of the stent ofFIG. 38, evidencing two stable inner tubes 194 for suction andapplication of glue.

FIG. 40 is a line drawing evidencing the angle of stent 112 tosemicircular finger 172.

FIG. 41 is a perspective view from an underneath angle of a wire stent112 comprising an integrated cuff 116, further evidencing a series ofclamping devices 196 circumnavigating the prosthetic annulus, each suchdevice clamping down a security belt 198.

FIG. 42 evidences a perspective view of a guidance catheter 144 locatedwithin the stent 112 pictured in FIG. 41, with wires 200 emanating fromholes around the catheter body 202 and attached through the prostheticannulus to the clamp devices (not pictured) pictured in FIG. 41.

FIG. 43 shows a closer view of the guide catheter 144, stent 112 andstrings 200 emanating from catheter holes 202, connecting to securitybelt clamps 196 as they secure security belt 198.

FIG. 44 shows an underneath view of the guidance catheter, string andstent assembly of FIGS. 41-43, evidencing the mechanism by which pullingthe strings 200 through the catheter holes 202 closes the clamp devices196 around the security belt 198.

FIG. 45 shows a close view from a perspective inside the stent of theguidance catheter, string and stent assembly of FIGS. 41-44, evidencinga cross-section of the guidance catheter 144 and a cross-section of theintegrated cuff 116, evidencing the perforation of the cuff by eachstring 200 and the connection of each string 200 to a clamping device196, which clamps security belt 198 into place.

Description of Improved Cuff/Collar FIGS.

Referring now to the FIGURES, FIG. 46 shows the atrial cuff/collar 116wherein the shape is somewhat mushroom shaped, or agaricoid. In thisembodiment, hemodynamic leaking is addressed wherein the atrialcuff/collar 116 has been constructed to have a tensioning ordownward-spring feature 204 in order to contour to the commissures of apathologically defective mitral valve and constructed to contour to thezone of coaptation of the pathologically defective mitral valve. Thecommissural contour components at each down-turned end of the atrialsealing gasket and the zone of coaptation contour components of theatrial cuff/collar 116 act to confirm to the saddle-shape wherein thecommissural contour components are in direct communication with themitral valve commissures, and the zone of coaptation contour componentsare in direct communication with the mitral valve zone of coaptation

FIG. 47 shows the atrial cuff/collar 116 wherein the shape is“fingernail shaped” or onychoid. In this embodiment, the truncatedportion is positioned during deployment adjacent to the aortic valvearea. The rounded portion then is seated and covers the posteriorcommissure while the truncated portion avoids obstruction by the lackingthe surplus of cuff material that would define an interfering structure.

FIG. 48 shows the atrial cuff/collar 116 wherein the shape is “kidneyshaped” or reniform. In this embodiment, the inner curve of the shape ispositioned during deployment to face the aortic valve area (anteriorly)and obstruction is avoided by the lack of an interfering structure. Incontrast, additional gasket material is provided so that the gasket maybe seated to cover both commissural areas of the mitral valve. The outercurve of the atrial cuff/collar 116 functions to prevent leakage nearthe zone of coaptation.

FIG. 49 shows the atrial cuff/collar 116 wherein the shape is an oval.In this embodiment, the anterior rounded portion 212 is positionedduring deployment adjacent to the aortic valve area and rises to travelalong the atrial wall to provide sealing without obstruction. Theposterior rounded portion 214 then is seated and covers the commissuresand seals against leaking.

FIG. 50 shows the atrial cuff/collar 116 wherein the shape is atruncated-oval having a squared, truncated portion 206. Similar to FIG.47, in this embodiment, the truncated portion 206 is positioned duringdeployment adjacent to the aortic valve area, but also comprises acurved aspect 216 that rises to travel along the atrial wall to providesealing without obstruction. The rounded portion 216 then is seated andcovers the posterior commissure while the truncated portion 206 avoidsobstruction by the lacking the surplus of cuff material that woulddefine an interfering structure.

FIG. 51 shows the atrial cuff/collar 116 as an acute (downward) anglesealing structure. In this embodiment, the atrial sealing gasket has atensioning or spring-like feature similar to FIG. 46, but with a atrialcuff profile that is about 1 cm or less. Although the small cuff/collar116 may have less ability to seal against leaking as a consequence ofits smaller size, the benefit of the smaller profile is that there isless wear, less movement, less inflammation, and less damage to theatrial tissue.

FIG. 52 shows the atrial cuff/collar 116 and the internal valve leafletsat nearly that same planar location/height. In this embodiment, thecuff/collar 116 allows the prosthetic valve leaflet assembly 118 to beseated within the mitral annulus at an optimum height, balancingavoiding LVOT obstruction below the annulus while providing the abilityto vary the functionality of the ventricular filling.

FIG. 53 shows the atrial cuff/collar 116 wherein the shape ispropeller-shaped. In this embodiment, the atrial cuff/collar 116 ispositioned during deployment such that where the gasket is at a minimum,the aortic valve area (anteriorly) has little or no pressure from theprosthetic valve 110 against the annular tissue adjacent the aorticvalve. In contrast, the “blades” of the propeller shape provideadditional cuff material so that the gasket may be seated to cover bothcommissural areas of the mitral valve. In this embodiment, no additionalcuff material is provided near the zone of coaptation and the nativeleaflets provide sufficient sealing against leaking. There may be two orthree “blades” in the propeller structure.

FIG. 54 shows the atrial cuff/collar 116 wherein the shape is cruciform.In this embodiment, the atrial cuff/collar 116 is positioned duringdeployment such that there is cuff material provided to place aspecified amount of pressure on the annular tissue adjacent the aorticvalve. Similar to FIG. 53, the “blades” of the propeller shape provideadditional cuff material so that the gasket may be seated to cover bothcommissural areas of the mitral valve.

FIG. 55 shows the atrial cuff/collar 116 wherein the shape ispetal-shaped having a plurality of flat radial covered loops. In thisembodiment, the atrial cuff/collar 116 and the internal valve leaflets118 are at nearly that same planar location/height allowing theprosthetic valve to be seated within the mitral annulus at an optimumheight, balancing avoiding LVOT obstruction below the annulus whileproviding the ability to vary the functionality of the ventricularfilling. In this embodiment, the use of multiple radial loops allows theatrial gasket to match the trabeculations of the atrial/annular tissuearea.

FIG. 56 shows the atrial cuff/collar 116 wherein the shape ispetal-shaped having a plurality of flat radial covered stellate loops.Similar to FIG. 55, in this embodiment, the use of multiple radial loopsallows the atrial gasket to match the trabeculations of theatrial/annular tissue area.

FIG. 57 shows the atrial cuff/collar 116 wherein the shape ispetal-shaped having s plurality of flat radial covered stellate loopsillustrating how they can travel longitudinally to effectuate sealing.

FIG. 58 shows the atrial cuff/collar 116 wherein the shape is irregularor amoeboid. This type of customized atrial cuff/collar may be usefulwhere a specific pathology or anatomy presents the need for a specificstructural solution.

FIG. 59 shows the atrial cuff/collar 116 wherein the shape iscup-shaped, or chair-shaped, known as cotyloid shaped. In thisembodiment, the anterior portion is positioned during deploymentadjacent to the aortic valve area and rises to travel along the atrialwall to provide sealing without obstruction. The posterior roundedportion then is seated and covers the commissures and seals againstleaking. Similar to FIG. 53, in this embodiment, no additional cuffmaterial is provided near the zone of coaptation and the native leafletsprovide sufficient sealing against leaking.

FIG. 60 shows the atrial cuff/collar 116 wherein the shape is a partialhalf-round fan-shape. Similar to FIG. 50, the rounded portion is seatedinto the valve annulus and covers the posterior commissure while themissing portion avoids obstruction by the lacking the surplus of gasketmaterial that would define an interfering structure.

FIG. 61 shows the atrial cuff/collar 116 with an upturned flat U-shapedplanar rectangle. In this embodiment, the “short” sides are positionedanteriorly and posteriorly while the upturned portions provide atensioning surface against the commissural area.

FIG. 62A shows a side view and FIG. 62B shows a front perspective viewof one embodiment showing the atrial cuff/collar 116 attached to thestent body at a forward angle, posterior to anterior.

Description of Improved Stent Figures

Referring now to the FIGURES, FIG. 63A is a perspective view of thesaddle shape of a native mitral valve leaflet structure or of aprosthetic valve leaflet structure according to the present invention.Thus, it becomes quickly apparent that a standard prosthetic valve madeonly of a straight tubular stent having flat bicuspid valve leafletswill impose structural, and therefore functional limitations on anyprior standard devices. FIG. 63B is a drawing of the three-dimensionalrelative position of the mitral valve compared to the X-Y-Z axis andshows that the mitral valve is aligned off-axis. Specifically, themitral valve is (reference is made to the FIG. 63B for a more accuratedescription) positioned left of center along the horizontal X-axis andslightly rotated around the X-axis, it is below center along thevertical Y-axis and rotated slightly clockwise around the Y-axis, and itis tipped slightly left to right around the Z-axis, all in a structurethat is roughly saddle-shaped. These teachings applied to thepreparation of a pre-configured/pre-contoured stent provide one of theimportant features of the present invention.

FIG. 63C is a drawing of a side view representation of a mitral valveshowing the range of movement of the anterior and posterior leafletsfrom closed to opened. The larger anterior leaflet (left) joins thesmaller posterior leaflet (right) at the beginning of ventricularsystole (contraction) and dashed lines represent the open mitral valveduring passive and active ventricular diastole (filling). As seen inFIG. 63C, the anterior and posterior leaflets extend ventricularly to asubstantial degree.

FIG. 63D is a graphical three-dimensional representation of a mitralvalve with approximate orientation and sizes in all three dimensions.FIG. 63D shows the saddle shaped valve to be an average size of about0.5 cm in height, about 6.0 cm from side to side, and about 1.5 cm inwidth. Of course, this varies by patient and may also vary due topathological condition. Thus, a prosthetic stent must take intoconsideration these factors to provide a prosthetic that is nearlyoptimized to function as a healthy, native mitral valve.

FIG. 64 is a drawing of the heart in cross-section showing thepositional relationship of the mitral and tricuspid valves to thepulmonic and aortic arteries. FIG. 64 shows mitral valve 218, tricuspidvalve 220, aortic valve 222, and pulmonic valve 224. FIG. 64 shows how aprosthetic mitral valve that does not have a tailored, pre-contouredshape can interfere with the operation of the other valves due tospatial hindrances.

FIG. 65A is a perspective drawing of one embodiment according to thepresent invention showing a prosthetic mitral valve 110 having akidney-shaped (epicyclic, cardioid) stent conformation 112 incross-section with an atrial cuff 116, shown here as opaque for stentdetail. Thus, having a kidney-shaped stent body is intended to addressLVOT (left ventricular outflow tract) obstruction and other spatialobstructions that would interfere with optimal valve function.Prosthetic valve leaflets 118 are shown in FIG. 65A as positioned downwithin the stent body 112 a specific distance from the top.

FIG. 65B is a perspective drawing of one embodiment according to thepresent invention illustrating a prosthetic mitral valve 110 having arounded-shape or oval-shape stent 112 conformation in cross-section withvalve leaflets 118 positioned towards the middle-point halfway up withinthe stent body 112, and with an atrial cuff 116, shown here as opaquefor stent detail.

FIG. 66 is a perspective drawing of one embodiment according to thepresent invention showing a prosthetic mitral valve 110 having acurved-tubular shape stent conformation 112 in cross-section with anatrial cuff 116, shown here as opaque for stent detail. By curving awayfrom possible spatial obstruction, this stent shape is also intended toaddress spatial valve or flow obstruction issues.

FIG. 67 is a perspective drawing of one embodiment according to thepresent invention showing a prosthetic mitral valve 110 having arounded-shape or oval-shape stent conformation 112 in cross-section withprosthetic valve leaflets 118 positioned high in the stent toward theatrial end of the stent body, and an atrial cuff 116, shown here asopaque for stent detail. FIG. 67 shows an embodiment having alow-profile as to the height of the device. This embodiment is intendedto have a stent body 112 that will remain substantially within theannular space and does not extend beyond the distance of the open nativevalve leaflets (not pictured). Further, having the prosthetic valveleaflets 118 positioned high within the stent body 112 providesadditional advantages over prosthetic valves where the prosthetic valveleaflets are located further down within the stent body.

FIG. 68 is a perspective drawing of one embodiment according to thepresent invention showing a prosthetic mitral valve 110 having a stentbody 112 made from both braided wire 228 (atrial end) and laser-cutmetal 226 (annular or ventricular end), and an uncovered atrial cuff116.

FIG. 69 is a perspective drawing of one embodiment according to thepresent invention showing a prosthetic mitral valve 110 having a stentbody 112 made from both laser-cut metal 226 (atrial end) and braidedwire 228 (annular or ventricular end), and without an atrial cuff.

As stated, the stent may be an expandable laser cut stent or anexpandable braided stent and may be constructed of Martensitic or superelastic metal alloys. The stent/valve assembly may be compressed alongits longitudinal axis and will fit into a catheter-based stent deliverysystem. When the stent/valve is delivered to the location where it is tobe installed, it is expelled from the catheter by an obturator anddeposited at the site where it is to be deployed.

The stent may include a plurality of tether attachments upon which atether may be connected. The leaflet assembly is a separate butintegrated structure that is disposed within the stent body. Leafletassembly functions to provide the structure upon which the valveleaflets or cusps are located. Leaflet assembly may be made entirely ofstabilized tissue or it may be a combination wire and tissue structure.It is contemplated as within the scope of the invention that differentqualities of stabilized tissue, i.e. thin or thick, structurally rigidor flexible as it may be, may be used for the different components ofthe cuff covering, the stent covering, the leaflet assembly and theleaflets.

Prosthetic heart valve may also include a cuff. In one embodiment, thecuff “wire form” is an extension of the stent itself, where the stenthas been heated and manipulated upon a form to create the extendedspindles of the flat, collar plate of the cuff. In another embodiment,the cuff “wire form” is made separate from the stent and attached as aflat collar plate with independent loops of wire that create lobes orsegments extending radially/axially around the circumference of theinner rim, the joint where the cuff meets the tubular stent.

As contemplated, the deployment of one embodiment of a prosthetic valveaccording to the present invention includes an embodiment of a deliverycatheter according to the present invention containing a pre-loadedprosthetic valve which is being pushed out of the delivery catheter,i.e. by an obturator, starting with (A) the valve completely within thecatheter, (B) the cuff portion being in view, (C) the stent bodyfollowing, and (D) the prosthetic valve with attached tethers forpositioning and/or adjustment and/or securing the valve to tissue.

Description of Narrow Gauge Stent Figures

Referring now to the FIGURES, FIG. 70 is a line drawing evidencing thenative mitral valve 218 without a prosthetic implant. Anterior leaflet230, posterior leaflet 232, anterolateral commissures 234 and posteriorcommissures 236 are shown. The tips of the anterior and posteriorcommissures have been marked for reference.

FIG. 71 shows how a prosthetic valve 110 that is sized solely based onthe native annulus results in an over-sized prosthetic valve thatstretches or tears the native commissures 234 and 236 open, preventingthem from performing their native sealing, which is often not overlyaffected in pathological conditions and may retain some native sealingfunction.

FIG. 72 shows how a prosthetic mitral valve 110 that is sized to avoidinteraction with or deformation of the commissures can be used to treatmitral regurgitation at the central jet, without having the solution,the valve, cause addition problems itself. Note how anterolateralcommissure 234 defined by P1-A1 portions of the leaflet remain intactfor sealing, and how posteromedial commissure 236 defined by P3-A3portions of the leaflet also remain intact for sealing.

FIG. 73 shows an even narrower diameter prosthetic valve 110 being used,especially in a functional mitral regurgitation patient that does notneed necessarily 100% sealing to achieve beneficial effects of theimplant. Note also that prosthetic valves may be configured to have 2-,3-, or 4-leaflet valve structures.

FIG. 74 shows how the hyperbolic paraboloid shape of the native mitralvalve yields different diameters, whether posterior to anterior, orlongitudinal along the line of the cusp interface. Here, the goal ofavoiding deformation of the commissural leaflets is exemplified, withoutnecessarily limiting the invention herein, as a mathematical ratiowhereby line a-a exemplifies a diameter that is too large, but that linec-c, across the cross-section of the leaflets, illustrates one preferredexample of the invention.

FIG. 75 shows how an over-large valve extends beyond line c-c, andcould, if the longest diameter were inadvertantly used, the fulldiameter of the native annulus line a-a, that it extends even furtherbeyond what is believed to be too large of a valve diameter (in somesituations).

FIG. 76 and FIG. 77 show positive examples of the concept disclosedherein, where the diameter is either equal to or less than thecross-section diameter of the native annulus from posterior to anteriorside.

FIG. 78 shows one non-limiting embodiment of the prosthetic valve 110which has been deployed in the native mitral annulus. FIG. 9 shows cuff116 and stent body 112, along with tethers 138 and epicardial anchor140. The dashed line illustrates how the present invention may beconstructed having a significantly narrower stent body that standardprosthetic valves of the this class, while maintaining standard-sizedcuff, internal valve assembly, and tether features.

In this embodiment of a prosthetic heart valve according to the presentinvention, there is a tubular stent having tether attachment structuresat one end and tubular stent is attached to cuff at the other end.Leaflet assembly (not shown) is disposed within stent and supportsleaflets (also not shown). Cuff has independent articulating loops ofwire and a covering.

As stated, tubular stent 112 may be an expandable laser cut stent or anexpandable braided stent. Tubular stent 112 may be constructed ofMartensitic or super elastic metal alloys. Tubular stent 112 may becompressed along its longitudinal axis and will fit into acatheter-based stent delivery system. When the tubular stent 112 isdelivered to the location where it is to be installed, it is expelledfrom the catheter by an obturator and deposited at the site where it isto be deployed.

Tubular stent 112 includes a plurality of tether attachments 138 uponwhich a tether, shown, may be connected. FIG. 78 shows an embodimenthaving three tether attachments 138 which are integrated into the distalportion of the stent. In this embodiment, the tethers extend from thestent, through the pericardial and epicardial tissue and are tied off ata pledget, button or similar type of anchor 140 on the outside of theheart. Such anchor 140 may itself be comprised of or covered withstabilized tissue.

Leaflet assembly 118 is a separate but integrated structure that isdisposed within the stent. Leaflet assembly 118 functions to provide thestructure upon which the valve leaflets or cusps are located. Leafletassembly 118 may be made entirely of stabilized tissue and/or polymericfabric, or it may be a combination wire and tissue/fabric structure.Where leaflet assembly is composed entirely of tissue, it iscontemplated that the leaflet assembly, leaflet support structure, andleaflets or cusps are made from tissue. It is contemplated as within thescope of the invention that different qualities of stabilized tissue,i.e. thin or thick, structurally rigid or flexible as it may be, may beused for the different components of the cuff covering, the stentcovering, the leaflet assembly and the leaflets. Where leaflet assembly118 is composed of wire and tissue, it contemplated that assembly orsupport(s), or both, may be made from wire, and the cusps wouldnecessarily be made from tissue.

In one embodiment, the cuff wire form 116 is an extension of the stent112, where the stent has been heated and manipulated upon a form tocreate the extended spindles of the flat, collar plate of the cuff. Inanother embodiment, the cuff wire form 116 is made separate from thestent 112 and attached as a flat collar plate constructed to include aninner rim and an outer rim, with independent loops of wire that createlobes or segments extending axially around the circumference of theinner rim, the joint where the cuff meets the tubular stent.

INCORPORATION AND EQUIVALENTS

The references recited herein are incorporated herein in their entirety,particularly as they relate to teaching the level of ordinary skill inthis art and for any disclosure necessary for the commoner understandingof the subject matter of the claimed invention. It will be clear to aperson of ordinary skill in the art that the above embodiments may bealtered or that insubstantial changes may be made without departing fromthe scope of the invention. Accordingly, the scope of the invention isdetermined by the scope of the following claims and their equitableEquivalents.

What is claimed is:
 1. A prosthetic heart valve for implantation in anative mitral valve annulus between a left atrium and a left ventricleof a heart, the prosthetic heart valve comprising: a self-expandingtubular stent having an atrial end and a ventricular end opposite theatrial end; a leaflet assembly, including a plurality of prostheticleaflets, disposed within and supported by the tubular stent; and acollar having a first end and a free end opposite the first end, thefirst end of the collar joined to the tubular stent at the ventricularend of the tubular stent, the collar at least partially surrounding thetubular stent, the collar having a diameter that increases from thefirst joined end of the collar toward the opposite free end of thecollar so that portions of the collar are spaced radially outwardly fromthe tubular stent, wherein, in an implanted condition of the prostheticheart valve, the collar is configured to be positioned within the nativemitral valve annulus so that annular tissue of the native mitral valveannulus exerts lateral pressure onto the collar, wherein the prostheticheart valve includes a plurality of tines circumferentially locatedaround the prosthetic heart valve, the plurality of tines configured toprovide attachment to tissue in the implanted condition of theprosthetic heart valve.
 2. The prosthetic heart valve of claim 1,wherein the tines are semi-circular hooks configured to pierce into theannular tissue of the native mitral valve annulus.
 3. The prostheticheart valve of claim 1, wherein the collar is formed from a web ofnitinol shape-memory material covered by at least one of a stabilizedtissue and a synthetic material.
 4. The prosthetic heart valve of claim1, wherein the collar is formed separately from the tubular stent. 5.The prosthetic heart valve of claim 1, wherein the collar is formed fromloops of wire.
 6. The prosthetic heart valve of claim 1, wherein thecollar is constructed from an attached panel formed of polyester fabricmaterial.
 7. The prosthetic heart valve of claim 1, wherein the collaris constructed from a panel that is perforated to provide a mesh-likesurface, and the tubular stent is constructed from a tube in whichregular cutouts are formed.
 8. The prosthetic heart valve of claim 1,wherein the tubular stent and the collar are integrally manufactured asa unitary stent-collar construction.
 9. The prosthetic heart valve ofclaim 1, wherein the collar is configured to prevent migration of theprosthetic heart valve into the left ventricle, and the plurality oftines are configured to prevent migration of the prosthetic heart valveinto the left atrium.
 10. The prosthetic heart valve of claim 1, whereinan interior of the tubular stent is lined with tissue.
 11. Theprosthetic heart valve of claim 1, wherein an exterior of the tubularstent is lined with either tissue or a synthetic material.
 12. Theprosthetic heart valve of claim 1, wherein the leaflet assembly isformed of bovine pericardial tissue.
 13. The prosthetic heart valve ofclaim 1, wherein the collar is flexible such that the collar is able toconform to irregularities of the shape of the native mitral valveannulus.
 14. The prosthetic heart valve of claim 13, wherein the collaris configured to provide a tight seal against tissue within the nativemitral valve annulus to prevent blood from leaking around the prostheticheart valve.
 15. The prosthetic heart valve of claim 14, wherein theprosthetic heart valve is configured to be secured in the native mitralvalve annulus by the plurality of tines without the use of tethers. 16.The prosthetic heart valve of claim 1, wherein the tubular stent and thecollar are both laser cut with pre-determined shapes to facilitatecollapsing into a catheter delivery system.
 17. The prosthetic heartvalve of claim 1, wherein the collar extends radially outward of anouter wall of the tubular stent, in an expanded condition of the tubularstent, between about 2 mm and about 10 mm.
 18. The prosthetic heartvalve of claim 1, wherein the collar includes a plurality of wirespindles.
 19. The prosthetic heart valve of claim 18, wherein theplurality of wire spindles are substantially uniform in shape and size.20. The prosthetic heart valve of claim 1, wherein the first end of thecollar is joined to the tubular stent at the ventricular end of thetubular stent to form a non-fatiguing elastic stent-collar joint capableof maintaining elastic compliance upon deployment of the prostheticheart valve.
 21. The prosthetic heart valve of claim 1, wherein theself-expanding tubular stent is formed of a nickel-titanium alloy, theplurality of prosthetic leaflets are formed of bovine pericardialtissue, and the collar is formed of a nickel-titanium alloy, the collarbeing formed as a separate component from the tubular stent, the collarbeing configured to locally contour to the native mitral valve annulusin the implanted condition of the prosthetic heart valve, the collaralso being configured to prevent displacement of the prosthetic heartvalve into the left ventricle.
 22. The prosthetic heart valve of claim21, wherein the diameter of the collar at the first joined end issubstantially equal to a diameter of the tubular stent at theventricular end of the tubular stent.
 23. The prosthetic heart valve ofclaim 22, wherein the collar includes a plurality of wire spindles. 24.The prosthetic heart valve of claim 23, wherein the plurality of wirespindles are substantially uniform in shape and size.
 25. The prostheticheart valve of claim 24, wherein the first end of the collar is joinedto the tubular stent at the ventricular end of the tubular stent to forma non-fatiguing stent-collar elastic joint capable of maintainingelastic compliance upon deployment of the prosthetic heart valve. 26.The prosthetic heart valve of claim 1, wherein the cuff extends at anangle of between about 60 degrees and about 150 degrees relative to anouter wall of the tubular stent.
 27. The prosthetic heart valve of claim26, wherein the collar extends radially outward of the outer wall of thetubular stent, in an expanded condition of the tubular stent, betweenabout 3 mm and about 30 mm.
 28. The prosthetic heart valve of claim 27,wherein a ratio (“H:L”) of a height (“H”) of the tubular stent in theexpanded condition of the tubular stent to a lateral distance (“L”) thatthe collar extends onto the annular tissue of the native mitral valveannulus, in the implanted condition of the prosthetic heart valve, isbetween 1:10 and 10:1.
 29. The prosthetic heart valve of claim 28,wherein the ratio (“H:L”) is about 1:2.
 30. The prosthetic heart valveof claim 28, wherein the ratio (“H:L”) is about 2:1.